30 results on '"HLA-A1 Antigen"'
Search Results
2. Lysis of human chondrosarcoma cells by cytolytic T lymphocytes recognizing a MAGE-A3 antigen presented by HLA-A1 molecules.
- Author
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Bluman EM, Coulie PG, Xiaojuan S, Machan J, Lin C, Meitner PA, Block JA, and Terek RM
- Subjects
- Antigen Presentation immunology, Bone Neoplasms pathology, Cell Line, Tumor, Chondrosarcoma pathology, Epitopes, Flow Cytometry, Humans, Interferon-gamma pharmacology, T-Lymphocytes, Cytotoxic drug effects, Antigens, Neoplasm immunology, Bone Neoplasms immunology, Chondrosarcoma immunology, HLA-A1 Antigen immunology, Immunotherapy methods, Neoplasm Proteins immunology, T-Lymphocytes, Cytotoxic immunology
- Abstract
Treatment of chondrosarcomas is limited to resection because these tumors are unresponsive to standard adjuvant treatments, such as chemotherapy and radiation. We have previously shown that high-grade chondrosarcomas express unspecified members of the Melanoma Antigen (MAGE) gene family. We show here that FS human chondrosarcoma (FS) cells express MAGE-A3 gene and HLA-A1 molecules. In vitro assays show that a cytolytic T-lymphocyte clone (CTL) specific for a MAGE-A3 peptide presented by HLA-A1 specifically lysed FS chondrosarcoma cells. Addition of antigenic peptide did not increase the susceptibility of FS cells to CTL mediated lysis, suggesting that HLA-A1 expression by the chondrosarcoma cells limited their susceptibility to lysis by the anti-MAGE-A3 CTL clone. Incubation of FS cells with 50 U/mL interferon-gamma increased surface expression of HLA class-I molecules, increased their susceptibility to lysis, and had no effect on MAGE-A3 gene expression. These results suggest that immunotherapy targeted against chondrosarcoma cells is possible., ((c) 2007 Orthopaedic Research Society.)
- Published
- 2007
- Full Text
- View/download PDF
3. Identification of the novel allele, HLA-A*01:234 , in the mother of a German cord blood donor
- Author
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K Dullinger, V Weisbach, B Hauck-Dlimi, J Zingsem, and J Strobel
- Subjects
genetic processes ,Immunology ,information science ,Mothers ,Blood Donors ,Histocompatibility Testing ,Biology ,German ,symbols.namesake ,Genetics ,Humans ,Immunology and Allergy ,natural sciences ,Allele ,Alleles ,HLA-A1 Antigen ,Sanger sequencing ,High-Throughput Nucleotide Sequencing ,Fetal Blood ,eye diseases ,language.human_language ,HLA-A ,Cord blood ,language ,symbols ,Female ,Identification (biology) - Abstract
HLA-A*01:234 was identified by next-generation sequencing and confirmed by Sanger sequencing.
- Published
- 2018
4. The novel HLA‐A*01 variant, HLA‐A*01:308N , detected by sequencing‐based typing
- Author
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Anne S. Hynne, Marte K. Viken, Bente I. Hopland, Line M. L. Boulland, and Tore Jensen
- Subjects
Genetics ,Immunology ,Sequence Analysis, DNA ,Human leukocyte antigen ,Biology ,HLA-A ,mental disorders ,Humans ,Point Mutation ,Immunology and Allergy ,sense organs ,Typing ,Sequence-based Typing ,skin and connective tissue diseases ,Alleles ,HLA-A1 Antigen - Abstract
One nucleotide changes in position 740 of HLA-A*01:01 result in a novel null-allele, HLA-A*01:308N.
- Published
- 2019
5. Nucleophosmin is recognized by a cytotoxic T cell line derived from a rectal carcinoma patient
- Author
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Eric Miller, Elin R. Sigurdson, Francesco M. Marincola, Rolf Swoboda, Rajasekharan Somasundaram, Dorothee Herlyn, Paul von Franzke, Laura Caputo, Klara Berencsi, Neal J. Meropol, and Douglas D. Taylor
- Subjects
Cancer Research ,medicine.medical_treatment ,Antigen presentation ,Breast Neoplasms ,Lymphocyte Activation ,Peripheral blood mononuclear cell ,Article ,Immune system ,Antigen ,Antigens, Neoplasm ,medicine ,Humans ,Cytotoxic T cell ,Melanoma ,Cells, Cultured ,HLA-A1 Antigen ,Antigen Presentation ,integumentary system ,Rectal Neoplasms ,business.industry ,Nuclear Proteins ,Cancer ,Immunotherapy ,medicine.disease ,Peptide Fragments ,CTL ,Oncology ,Immunology ,Female ,Colorectal Neoplasms ,business ,Nucleophosmin ,T-Lymphocytes, Cytotoxic - Abstract
Immunotherapy of colorectal carcinoma (CRC) has great promise as the presence of T lymphocytes in CRC tissues in situ is correlated with reduced recurrence and increased survival. Thus, identification of the antigens recognized by T cells of CRC patients may permit development of vaccines with potential benefit for these patients. Using expression cloning, we identified the antigen, nucleophosmin (Npm), recognized by an HLA-A1 restricted cytotoxic T lymphocyte (CTL) line derived from the peripheral blood mononuclear cells (PBMC) of a rectal cancer patient. A decamer peptide derived from the Npm sequence sensitized peptide-pulsed HLA-A1 positive cells to lysis by the CTL line. The peptide also induced proliferative and cytotoxic T lymphocytes in the PBMC of 4 of 6 CRC patients, which lysed HLA-A1 positive peptide-pulsed target cells and CRC cells endogenously expressing Npm. Overexpression of Npm by tumors of various histological types, recognition of the antigen by T cells derived from different CRC patients and association of the antigen with poor prognostic outcome make it a promising target for immunotherapeutic intervention in cancer patients.
- Published
- 2009
6. Soluble Human Leukocyte Antigen class I antigen and interleukin-12 in hepatectomized patients
- Author
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Tatsuo Shimura, Masatoshi Ishizaki, Tsutomu Kobayashi, Nobuhiro Morinaga, Hideki Suzuki, Hiroyuki Kuwano, and Kenichiro Araki
- Subjects
Liver Cirrhosis ,medicine.medical_treatment ,Enzyme-Linked Immunosorbent Assay ,Pharmacology ,Plasma ,Adjuvants, Immunologic ,Antigen ,medicine ,Hepatectomy ,Humans ,Cytotoxic T cell ,Postoperative Period ,Receptor ,HLA-A1 Antigen ,Aged ,business.industry ,Transfusion Reaction ,General Medicine ,Middle Aged ,Natural killer T cell ,Interleukin-12 ,CTL ,Solubility ,Case-Control Studies ,Immunology ,Interleukin 12 ,Surgery ,Fresh frozen plasma ,business - Abstract
Background: Interleukin-12 (IL-12) has been shown to enhance the cytotoxic activity of NK cells and CTL. IL-12 also acts as a growth factor for activated NK, T and NKT cells. The soluble HLA class I (sHLA-I) has been reported to bind a killer-cell inhibitory receptor, which is expressed on the NK cell, and its signals inhibit NK cell-mediated cytotoxicity. Effects of fresh frozen plasma (FFP) on post-operative immune status have not yet been completely examined. Methods: Thirty consecutive patients taking a hepatectomy were enrolled. The levels of IL-12 and sHLA-I were examined by enzyme-linked immunosorbent assay. Results: The rate of complication after hepatectomy in the FFP-administered patients was higher than that in patients without FFP administration (P= 0.0358). Decreased IL-12 levels after surgery in patients without FFP administration recovered to the preoperative state earlier than those in patients with FFP administration (P < 0.05). The levels of sHLA-I in the FFP-administered patients were higher than those in the patients without FFP administration (P < 0.05). Conclusions: Administration of FFP, which contains sHLA-I, affected the levels of sHLA-I after hepatectomy. Both high levels of sHLA-I and low levels of IL-12 could attenuate NK activities after hepatectomy, especially when FFP would be administered.
- Published
- 2009
7. Alloantibodies that React with Subsets of Human T Cells
- Author
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Aad van Leeuwen
- Subjects
Adult ,Erythrocytes ,Rosette Formation ,T cell ,Immunology ,Biochemistry ,HLA-B8 Antigen ,HLA-DR3 Antigen ,HLA Antigens ,Isoantibodies ,Pregnancy ,T-Lymphocyte Subsets ,Genetics ,medicine ,Animals ,Humans ,Immunology and Allergy ,Hla antibodies ,HLA-A1 Antigen ,Antilymphocyte Serum ,B-Lymphocytes ,Sheep ,biology ,Chemistry ,Homozygote ,Receptors, Antigen, T-Cell, gamma-delta ,HLA-DR Antigens ,General Medicine ,Cytotoxicity Tests, Immunologic ,Molecular biology ,medicine.anatomical_structure ,Histocompatibility ,biology.protein ,Female ,Immunization ,Antibody - Abstract
Using the two color fluorescence (TCF) method, alloantibodies against subsets of T cells could be detected in sera from pregnant women with strong HLA antibodies. To preclude interference of these HLA antibodies with the recognition of the T cell antibodies, serum donors were selected which were HLA-Al, -B8, -DRw3. Their sera were tested on a panel of individuals homozygous for HLA-Al, -B8, -DRw3. By enriching peripheral mononuclear blood lymphocytes for Tgamma cells it could be shown that some of the sera reacted mainly with Tgamma and others with Tmu lymphocytes, while some sera reacted with both.
- Published
- 2008
8. HLA-A, B, C and DR antigens in immunoglobulin A deficiency
- Author
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C. I. E. Smith and Lennart Hammarström
- Subjects
Immunology ,HLA-DR3 ,Human leukocyte antigen ,Selective IgA deficiency ,Biochemistry ,HLA-B8 Antigen ,HLA-DR3 Antigen ,Antigen ,HLA Antigens ,Genetics ,Humans ,Immunology and Allergy ,Medicine ,Typing ,HLA-A1 Antigen ,HLA-A Antigens ,business.industry ,Histocompatibility Antigens Class II ,IgA Deficiency ,HLA-DR Antigens ,General Medicine ,medicine.disease ,HLA-A ,Immunoglobulin A deficiency ,Dysgammaglobulinemia ,business - Abstract
HLA-A, B, C and DR typing was performed in 21 unrelated healthy blood donors with selective IgA deficiency (< 0.02 G/l of IgA). A significant increase in HLA A1 (P < 0.05), HLA B8 (P < 0.01) and HLA DR3 (P < 0.001) was found. The frequency of HLA A28 was also increased (P < 0.05). Furthermore, HLA A28 was present in all four donors lacking DR3.
- Published
- 2008
9. The HLA-A1-B8 haplotype hitchhiking with the hemochromatosis mutation: does it affect the phenotype?
- Author
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Norbeth Hansson, Bernd Ritter, and K. Sigvard Olsson
- Subjects
Adult ,Male ,Locus (genetics) ,Human leukocyte antigen ,HLA-A3 Antigen ,HLA-B8 Antigen ,medicine ,Humans ,Porphyria cutanea tarda ,Cysteine ,Hemochromatosis Protein ,HLA-A1 Antigen ,Hemochromatosis ,Aged ,Sweden ,Genetics ,biology ,Transferrin saturation ,HLA A1-B8 haplotype ,Histocompatibility Antigens Class I ,Haplotype ,Membrane Proteins ,Iron Deficiencies ,Hematology ,General Medicine ,Middle Aged ,medicine.disease ,Pedigree ,Ferritin ,Phenotype ,Haplotypes ,Ferritins ,Mutation ,Immunology ,biology.protein ,Tyrosine ,Female - Abstract
Background: Hemochromatosis is a recessively inherited disorder caused by a point mutation, C282Y of the HFE gene on chromosome 6p21.3 near the human leukocyte antigen (HLA) locus. It is unknown why some homozygotes develop a severe iron loading, while others do not. A recent study suggested that the A1-B8 haplotype may be associated with higher iron storage. Methods: We studied HLA haplotypes of 85 probands, 31 females and 54 males, and their family members from a rural population where A1-B8 was common. We tested the hypothesis of a modifying effect of the A1-B8 haplotype. Results: Most homozygotes had a mild phenotypic expression, and were often detected accidentally because of a laboratory routine including transferrin saturation. A disease-related morbidity [serum alanine aminotransferase (S-ALT) > 43 U] was present in 40%.Three had porphyria cutanea tarda. Two brothers with A1-B8 died of bronze diabetes, probably caused by co-inheritance of congenital spherocytosis. In females there were no significant differences in phenotypic expression between groups with regard to the presence or absence of A1-B8. Two females
- Published
- 2007
10. Association of human leukocyte antigen ancestral haplotype 8.1 with adverse outcome of non-Hodgkin's lymphoma
- Author
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Krzysztof Warzocha, Gilles Salles, Renata Mika-Witkowska, Przemysław Biliński, Małgorzata Zajko, Jacques Bienvenu, Bertrand Coiffier, Przemyslaw Juszczynski, Jacek Nowak, and Ewa Kalinka-Warzocha
- Subjects
Male ,Oncology ,Lymphotoxin alpha ,Cancer Research ,medicine.medical_specialty ,Linkage disequilibrium ,Lymphoma, B-Cell ,Time Factors ,HLA-C Antigens ,Human leukocyte antigen ,Biology ,Cohort Studies ,International Prognostic Index ,Gene Frequency ,HLA Antigens ,HLA-DQ Antigens ,Internal medicine ,Genetics ,medicine ,HLA-DQ beta-Chains ,Humans ,Allele ,HLA-A1 Antigen ,Sequence Deletion ,HLA-A Antigens ,Tumor Necrosis Factor-alpha ,Lymphoma, Non-Hodgkin ,Haplotype ,HLA-DR Antigens ,Middle Aged ,medicine.disease ,Lymphoma ,Non-Hodgkin's lymphoma ,Survival Rate ,Treatment Outcome ,Immunology ,Female ,HLA-DRB1 Chains - Abstract
Previous reports have implicated the tumor necrosis factor (TNF� 308) locus to non-Hodgkin’s lymphoma (NHL) outcome. The purpose of the study was to examine other chromosome components of the HLA 8.1 ancestral haplotype (AH) and their relation to the clinical course of NHL. HLA class I, II, TNF� 308, and lymphotoxin alpha (LTA+252) alleles were analyzed in 154 newly diagnosed NHL patients. Three locus haplotypes were inferred from the unphased genotypes by a Bayesian implementation of the expectation maximization (EM) algorithm using the PHASE 2.1 program. TNF� 308A was the only allele associated with fever, poor performance status, elevated b2-microglobulin, TNF and its p75 receptor plasma levels. Although TNF� 308A was in strong linkage disequilibrium with the remaining alleles of 8.1 AH, only HLA-A*01 and HLA-B*08 showed association with prognostic variables. A part of 8.1 AH (A*01-B*08-TNF� 308A) was predictive for shorter freedom from progression and overall survival (RR ¼ 2.47, P ¼ 0.041; RR ¼ 3.15; P ¼ 0.0049), an association that was stronger than TNF� 308A alone and independent from International Prognostic Index (RR ¼ 1.55, P < 0.001; RR ¼ 2.36; P < 0.0001). A*01-B*08-TNF� 308A fragment of 8.1AH remained an independent predictive factor in a multivariate model. We conclude that 8.1 AH is an important contributor to NHL outcome. In contrast to A*01-B*08-TNF� 308A, the remaining alleles (Cw*07, DRB1*03, LTA+252G) associated with the 8.1 AH seem to be its passive components. V C 2007 Wiley-Liss, Inc.
- Published
- 2007
11. Cancer/testis antigen expression and specific cytotoxic T lymphocyte responses in non small cell lung cancer
- Author
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Lukas Bubendorf, Célia Groeper, Franco Gambazzi, Giulio C. Spagnoli, Hans-Reinhard Zerkowski, Michael Heberer, Rachel Rosenthal, Michel Adamina, and Paul Zajac
- Subjects
Male ,endocrine system ,Cancer Research ,Lung Neoplasms ,Molecular Sequence Data ,Gene Expression ,Biology ,Epitope ,Lymphocytes, Tumor-Infiltrating ,Antigen ,Antigens, Neoplasm ,Carcinoma, Non-Small-Cell Lung ,HLA-A2 Antigen ,Humans ,Cytotoxic T cell ,Amino Acid Sequence ,neoplasms ,HLA-A1 Antigen ,Aged ,HLA-A Antigens ,Immunodominant Epitopes ,Reverse Transcriptase Polymerase Chain Reaction ,Tumor-infiltrating lymphocytes ,Antibodies, Monoclonal ,Membrane Proteins ,Dendritic Cells ,Middle Aged ,Immunohistochemistry ,Peptide Fragments ,Neoplasm Proteins ,CTL ,Oncology ,Immunology ,Cancer research ,Cancer/testis antigens ,Female ,Melanoma-Specific Antigens ,CD8 ,T-Lymphocytes, Cytotoxic - Abstract
Non small cell lung cancers (NSCLC) express cancer/testis antigens (CTA) genes and MAGE-A expression correlates with poor prognosis in squamous cell carcinomas. We addressed cytotoxic T lymphocytes (CTL) responses to HLA class I restricted CTA epitopes in TIL from NSCLC in an unselected group of 33 patients consecutively undergoing surgery. Expression of MAGE-A1, -A2, -A3, -A4, -A10, -A12 and NY-ESO-1 CTA genes was tested by quantitative RT-PCR. Monoclonal antibodies (MAb) recognizing MAGE-A and NY-ESO-1 CTA were used to detect CTA by immunohistochemistry. CD8(+) TIL obtained from tumors upon culture with anti CD3 and anti CD28 mAb and IL-2 were stimulated with autologous mature DC (mDC) and HLA-A*0101 restricted MAGE-A1(161-169) or MAGE-A3(168-176) peptides or HLA-A*0201 restricted MAGE-A4(230-239), MAGE-A10(254-262), NY-ESO-1(157-165) or multi-MAGE-A (YLEYRQVPV) peptides or a recombinant vaccinia virus (rVV) encoding MAGE-A and NY-ESO-1 HLA-A*0201 restricted epitopes and CD80 co-stimulatory molecule. Specificity was assessed by (51)Cr release and multimer staining. At least one CTA gene was expressed in tumors from 15/33 patients. In 10 specimens, at least 4 CTA genes were concomitantly expressed. These data were largely confirmed by immunohistochemistry. TIL were expanded from 26/33 specimens and CTA-specific CTL activity was detectable in 7/26 TIL. In 6, however, specific cytotoxicity was weak, (40% lysis at a 50:1 E:T ratio) and multimer staining was undetectable. In one case, high (60% lysis at 50:1 E:T ratio) MAGE-A10(254-262) specific, HLA-A*0201 restricted response was observed. Supportive evidence was provided by corresponding multimer staining. Although CTA genes are frequently expressed in NSCLC, detection of CTL reactivity against CTA epitopes in TIL from nonimmunized NSCLC patients represents a rare event.
- Published
- 2006
12. A mutated HLA-A*0101 allele in the colorectal cell line HCA-7
- Author
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David C. Bicknell and Walter F. Bodmer
- Subjects
DNA Repair ,Base Pair Mismatch ,Base pair ,Immunology ,Biology ,medicine.disease_cause ,Polymerase Chain Reaction ,Biochemistry ,Cytosine ,chemistry.chemical_compound ,Exon ,Gene Frequency ,Cell Line, Tumor ,HLA-A2 Antigen ,Genetics ,medicine ,Humans ,Immunology and Allergy ,Cloning, Molecular ,Promoter Regions, Genetic ,3' Untranslated Regions ,Alleles ,HLA-A1 Antigen ,DNA Primers ,Mutation ,HLA-A Antigens ,Reverse Transcriptase Polymerase Chain Reaction ,DNA ,Exons ,Sequence Analysis, DNA ,General Medicine ,Molecular biology ,chemistry ,RNA splicing ,RNA ,DNA mismatch repair ,Isoelectric Focusing ,Primer (molecular biology) ,Colorectal Neoplasms - Abstract
The colorectal cell line HCA-7 expresses surface human leucocyte antigen-A*0201 (HLA-A*0201), but lacks expression of HLA-A*0101 whilst the normal B-cell line (EVA-1224), derived from the same individual, expresses both surface HLA-A1 and HLA-A2. Amplification refractory mutation system-polymerase chain reaction analysis, using sequence-specific primers, suggested that HCA-7 has a mutation in a 7 base pair (bp) cytosine repeat sequence located at the beginning of Exon 4 (bp 621-627). Cloning and sequencing revealed HCA-7 to have eight cytosine residues in this repeat sequence. In contrast, EVA-1224 contained only 7 cytosines. Analysis of the mRNA for HLA-A*010 using reverse trancriptase-polymerase chain reaction (RT-PCR), with an allele-specific 5' primer in exon 2 (bp 253-271) and a series of 3' primers in exons 3, 4 and 7 and in the 3'untranslated region, revealed that HCA-7 contained a shortened message terminating in the region of the exon 3/4 boundary. The insertion of an extra cytosine in this region, which is only two bases from the exon 3/4 splice site, is presumed to lead to a splicing defect between exons 3 and 4 resulting in the lack of expression of a functional HLA-A*0101 product. HCA-7 is mismatch repair (MMR) defective due to lack of expression of hMLH1 resulting from hypermethylation of the promoter region. The consequential increase in errors in single-nucleotide repeat stretches of DNA can account for the HLA-A*0101 mutation. This has probably then been selected for in the tumour to enable escape from immune attack against an HLA-A*0101-restricted tumour-specific determinant that has also arisen as a result of the tumour being MMR defective.
- Published
- 2005
13. Analysis of CD8 T cell reactivity to cytomegalovirus using protein-spanning pools of overlapping pentadecapeptides
- Author
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Ines Kretzschmar, Florian Kern, Rudolf Volkmer-Engert, Nicole Faulhaber, Susanna Prösch, Constanze Schönemann, Petra Reinke, Claudia Frömmel, Elham Khatamzas, and Hans-Dieter Volk
- Subjects
Human cytomegalovirus ,Molecular Sequence Data ,Immunology ,Cytomegalovirus ,Peptide ,Human leukocyte antigen ,CD8-Positive T-Lymphocytes ,Biology ,Peripheral blood mononuclear cell ,Epitope ,HLA-B8 Antigen ,Immediate-Early Proteins ,Flow cytometry ,Viral Matrix Proteins ,HLA-B7 Antigen ,Interferon-gamma ,Viral Proteins ,HLA-A2 Antigen ,medicine ,Humans ,Immunology and Allergy ,Cytotoxic T cell ,Amino Acid Sequence ,HLA-A1 Antigen ,chemistry.chemical_classification ,medicine.diagnostic_test ,Phosphoproteins ,medicine.disease ,Virology ,Amino acid ,chemistry ,Cytomegalovirus Infections ,Peptides - Abstract
The frequencies of human cytomegalovirus (HCMV) protein-specific CD8 T cells, identified by the presence of intracellular IFN-gamma, were measured by flow cytometry following stimulation of freshly isolated peripheral blood mononuclear cells (PBMC) with comprehensive peptide pools. These pools spanned the entire amino acid sequences of the HCMV pp65 and major immediate early (IE-1) proteins and consisted of 15-amino acid peptides with at least nine overlaps between neighboring peptides. As a result all potential CD8 T cell epitopes contained in these proteins were provided by the complete pools and, therefore, unlike with single epitopes, testing was independent of donor HLA type. Individual stimulating peptides from the same pools were identified in parallel experiments. Thus we found that our results with the complete pools using PBMC from 26 healthy HCMV-seropositive donors were 100% sensitive and specific with respect to predicting the presence of recognized epitopes in the respective proteins. In addition, cells from 15 renal transplant patients were tested with complete pools alone. While our results confirmed our previous contention that HCMV IE-1 is an important CD8 T cell target, the technical improvement we made in order to address this question has clearly wider implications. Similar pools may be applied to examine the role of proteins from other pathogens, in autoimmune disease or following vaccination.
- Published
- 2000
14. The genetic basis for the association of the 8.1 ancestral haplotype (A1, B8, DR3) with multiple immunopathological diseases
- Author
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Martyn A. French, Simon Mallal, C.C. Kok, Frank T. Christiansen, David Sayer, Michael J. Garlepp, Richard J.N. Allcock, Patricia Price, and Campbell S. Witt
- Subjects
Genetics ,Candidate gene ,biology ,Common variable immunodeficiency ,Immunology ,Haplotype ,Disease ,Immunogenetics ,medicine.disease ,Major histocompatibility complex ,HLA-B8 Antigen ,HLA-DR3 Antigen ,Immune system ,Haplotypes ,Immune System Diseases ,medicine ,biology.protein ,Animals ,Humans ,Immunology and Allergy ,Allele ,HLA-A1 Antigen - Abstract
An individual's major histocompatibility complex (MHC) ancestral haplotype (AH) is the clearest single determinant of susceptibility to MHC associated immunopathological disease, as it defines the alleles carried at all loci in the MHC. However, the direct effects of any of the 150-200 genes that constitute the MHC are difficult to determine since recombination only occurs at defined hotspots. This review concerns the 8.1 AH (HLA-A1, C7, B8, C4AQ0, C4B1, DR3, DQ2), which is carried by most Caucasians with HLA-B8. It is associated with accelerated human immunodeficiency virus (HIV) disease, and susceptibility to insulin-dependent diabetes mellitus (IDDM), systemic lupus erythematosus, dermatitis herpetiformis, common variable immunodeficiency and IgA deficiency, myasthenia gravis and several other conditions. We have mapped susceptibility genes for HIV, IDDM and myasthenia gravis to the central MHC between HLA-B and the tumour necrosis factor or complement genes. Here we consider which of the remaining 8.1-associated diseases are more closely associated with HLA-DR3 and/or DQ2. Several candidate genes in the central MHC have the potential to modulate immune or inflammatory responses in an antigen-independent manner, as is seen in studies of cultured cells from healthy carriers of the 8.1 AH. Hence these genes may act as a common co-factor in the diverse immunopathological conditions associated with the 8.1 AH.
- Published
- 1999
15. HLA antigens in schistosomal hepatic fibrosis patients with haematemesis
- Author
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A. Shaltout, L. Montaser, L. Asser, M A Hagras, S. Wasfy, M. El Sawy, and H. Abaza
- Subjects
Adult ,Adolescent ,Immunology ,Helminthiasis ,Schistosomiasis ,Human leukocyte antigen ,Biochemistry ,Antigen ,HLA Antigens ,Fibrosis ,Genetics ,medicine ,Humans ,Immunology and Allergy ,Typing ,HLA-A1 Antigen ,business.industry ,Hepatobiliary disease ,Hematemesis ,General Medicine ,Middle Aged ,medicine.disease ,Schistosomiasis mansoni ,HLA-B Antigens ,Splenomegaly ,business ,Hepatic fibrosis ,Hepatomegaly - Abstract
20 patients of schistosomal hepatic fibrosis and splenomegaly (SHF) with and without haematemesis were examined. Typing for HLA-A, B and C antigens in these patients were compared with those of a group of 100 Egyptian controls. The study showed the presence of an association between HLA-A1 and B5 antigens in SHF cases. However, there was no significant association between HLA antigens and SHF cases with haematemesis.
- Published
- 2008
16. HLA antigens in leprosy patients
- Author
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Mehta Mm, K. K. Koticha, Bhatia Hm, Contractor Nm, and Uma M. Bale
- Subjects
business.industry ,HLA-B40 Antigen ,Immunology ,India ,General Medicine ,Human leukocyte antigen ,medicine.disease ,Biochemistry ,Phenotype ,HLA Antigens ,HLA-B Antigens ,Leprosy ,Genetics ,medicine ,Humans ,Immunology and Allergy ,business ,HLA-A1 Antigen - Published
- 2008
17. Selective IgA deficiency and hypoplenism
- Author
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B. H. Ramsahoye, W. Mumar-Bashi, S. H. Lim, and R. Evely
- Subjects
Adult ,medicine.medical_specialty ,business.industry ,IgA Deficiency ,Hematology ,Selective IgA deficiency ,medicine.disease ,Autoimmune Diseases ,HLA-B8 Antigen ,HLA-DR3 Antigen ,Endocrinology ,Haplotypes ,Internal medicine ,Immunology ,medicine ,Humans ,Female ,business ,HLA-A1 Antigen ,Splenic Diseases ,Ultrasonography - Published
- 2008
18. Tumour necrosis factor β gene polymorphisms in myasthenia gravis
- Author
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I. Torrente, M. M. Lino, P. Tonali, Anna Paola Batocchi, Amelia Evoli, Giovanni Zelano, and Daniela Settesoldi
- Subjects
Male ,Lymphotoxin alpha ,medicine.medical_specialty ,Thymoma ,Genotype ,Immunology ,Biology ,Gastroenterology ,HLA-B8 Antigen ,Pathogenesis ,HLA-DR3 Antigen ,Internal medicine ,Myasthenia Gravis ,Genetics ,medicine ,Humans ,Allele ,Lymphotoxin-alpha ,Alleles ,HLA-A1 Antigen ,Autoimmune disease ,Histocompatibility Testing ,medicine.disease ,Myasthenia gravis ,Settore MED/26 - NEUROLOGIA ,Phenotype ,Female ,Thymus Hyperplasia ,Thymus hyperplasia ,Polymorphism, Restriction Fragment Length - Abstract
Genetic analyses indicate that genes within the major histocompatibility complex (MHC) can be involved in susceptibility to autoimmune disease. To investigate the role of the tumour necrosis factor beta (TNFB) gene in myasthenia gravis (MG) susceptibility, we analysed an NcoI polymorphism within the TNFB gene in 63 MG patients and 93 healthy individuals. When patients were subdivided according to thymic pathology, we found differences between MG patients with thymic hyperplasia and thymoma versus controls. In MG patients with thymic hyperplasia we found a positive association with the TNFB*1 allele [Relative risk (RR): 2.6; P < 0.001] and phenotype (RR: 1.8; P < 0.005) and a negative association with the TNFB*2/2 genotype (RR: 0.2; P < 0.001) when compared to the controls. On the other hand, in MG patients with thymoma we found a positive association with the TNFB*2/2 genotype (RR: 5.6; P < 0.01) and a negative association with the TNFB*1 allele (RR: 0.3; P < 0.05) and *1/2 genotype (RR: 0.2; P < 0.01). These data suggest that the two different forms of MG can have different pathogenesis and that the TNFB gene could influence susceptibility to MG.
- Published
- 1998
19. A deletion in exon 3 results in a new HLA-A*01 null allele (A*0115N) in a Martinican woman
- Author
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L. Gebuhrer, A Assaqa, P Belon, Valérie Dubois, I. Favre-Victoire, and O. Béra
- Subjects
Molecular Sequence Data ,Immunology ,Fixed allele ,Biology ,Biochemistry ,Exon ,Genetics ,Humans ,Immunology and Allergy ,Martinique ,Allele ,Allele frequency ,Alleles ,HLA-A1 Antigen ,Sequence Deletion ,Base Sequence ,HLA-A Antigens ,Exons ,General Medicine ,C957T ,Null allele ,Molecular biology ,HLA-A ,Female ,Sequence Alignment - Abstract
We report the identification of a new HLA-A null allele, HLA-A*0115N. This null allele has been identified within the A*01 group by a combination of serological and molecular typing [Polymerase chain reaction (PCR) sequence-specific primers, PCR sequence-specific oligoprobes and sequence-based typing (SBT)] in a potential intrafamilial bone marrow donor from Martinique (French West Indies). To characterize this A*01 null allele, we performed DNA typing by PCR-SBT on genomic DNA from the beginning of exon 2 (position 84) through the end of the exon 4 (position 895) and revealed a nucleotide deletion at the end of the exon 3. This sole difference between the new allele and the HLA-A*0101 generates a premature stop codon (TGA) in the beginning of exon 4. This deletion most likely explains the lack of cell surface expression of the encoded protein despite the presence of A*01 allele. The absence of correct expression of the antigen on the cell surface was confirmed by one-dimensional isoelectric focusing (1D-IEF). To date, this is the fourth null allele described within the A*01 group.
- Published
- 2006
20. Identification of a sperm protein 17 CTL epitope restricted by HLA-A1
- Author
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Emanuela Salati, Maurizio Chiriva-Internati, Seah H. Lim, Stephanie Pochopien, and Zhiqing Wang
- Subjects
Cytotoxicity, Immunologic ,Male ,Cancer Research ,Peptide ,Biology ,Epitope ,law.invention ,Epitopes ,Antigen ,law ,In vivo ,Humans ,Cytotoxic T cell ,HLA-A1 Antigen ,chemistry.chemical_classification ,Dendritic Cells ,Spermatozoa ,Virology ,Molecular biology ,Peptide Fragments ,CTL ,Oncology ,chemistry ,Recombinant DNA ,CD8 ,T-Lymphocytes, Cytotoxic - Abstract
Sperm protein 17 (Sp17) is a novel cancer-testis antigen. We previously reported the successful generation of Sp17-specific HLA-A1-restricted cytotoxic T-lymphocytes (CTLs) from the peripheral blood of a healthy donor using a recombinant Sp17 protein. These CTLs were able to kill not only target cells pulsed with the recombinant protein but also fresh Sp17+ tumor cells. In the present study, we have identified a nonapeptide sequence within the Sp17 protein that is predicted to have a high binding affinity for the HLA-A1 molecules. We generated the synthetic nonapeptide and successfully propagated a peptide-specific CTL line. We confirmed that peptide Sp17103–111 (ILDSSEEDK) contains an Sp17 CTL epitope restricted by HLA-A1 and identified amino acid residues 104, 107, 109 and 110 as crucial for the CTL lysis. Our findings therefore provide the tool for the characterization of CD8 T-cell function in vivo and generation of epitope-specific treatment strategies. © 2003 Wiley-Liss, Inc.
- Published
- 2003
21. Recognition of HLA-A1 by murine monoclonal antibodies
- Author
-
Suzanne Salvi, Françoise Hartmann, Donata Rimoldi, and Stefan Carrel
- Subjects
medicine.drug_class ,Immunology ,Radioimmunoassay ,Mast-Cell Sarcoma ,chemical and pharmacologic phenomena ,Biology ,Monoclonal antibody ,Biochemistry ,Mice ,Antigen ,Tumor Cells, Cultured ,Genetics ,Splenocyte ,medicine ,Animals ,Humans ,Immunology and Allergy ,Melanoma ,HLA-A1 Antigen ,Mice, Inbred BALB C ,Antibodies, Monoclonal ,Mastocytoma ,General Medicine ,Transfection ,Flow Cytometry ,medicine.disease ,Precipitin Tests ,Virology ,Histocompatibility ,Immunoglobulin M ,Cell culture ,Immunoglobulin G ,Colonic Neoplasms ,biology.protein ,Antibody - Abstract
Balb/c mice were immunized with cells from the mouse mastocytoma line P815 transfected with an HLA-A1 gene. The splenocytes of the immunized mice were fused with cells from the murine myeloma NS-1. In an initial screening, supernatants of growing cultures were tested for their binding capacity to the immunizing P815/A1+ cells as well as to P815/A2+ cells. Three out of 756 hybrids produced antibodies which bound to P815/A1+ cells only. They were cloned and further analyzed for their binding reactivity to reference B-lymphoblastoid cells from the Tenth International Histocompatibility Workshop. One monoclonal antibody, designated 6B11, reacted only with HLA-A1+ cells, while the two other antibodies, 3G3 and 7F10, appeared to detect antigenic determinants shared by HLA-A1, A3, A11, A26, and A30 (3G3) and by HLA-A1, A3, A11, A26, A28 and A30 (7F10). Flow cytometric studies on B-lymphoblastoid cell lines as well as on a series of tumor cell lines, including melanoma and colon carcinoma lines, confirmed the specificity of these antibodies. Monoclonal antibodies 7F10 and 6B11 were found to be of the IgM class and 3G3 of the IgG1 class. By complement-dependent 51Cr release experiments it was further shown that the two IgM antibodies 7F10 and 6B11 were able to lyse all cell lines of the HLA-A1 haplotype tested.
- Published
- 1994
22. Nucleotide sequences of the variable regions of a human monoclonal antibody against HLA-A1, A23, and A24
- Author
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Takuji Ichihashi, Ryuzo Ohno, Kazuaki Kubo, and Tomoki Naoe
- Subjects
Silent mutation ,Molecular Sequence Data ,Immunology ,Immunoglobulin Variable Region ,HLA-A24 Antigen ,Complementarity determining region ,Biology ,Immunoglobulin light chain ,Polymerase Chain Reaction ,Biochemistry ,Homology (biology) ,Germline mutation ,Antibody Specificity ,Genetics ,Humans ,Immunology and Allergy ,Gene family ,Amino Acid Sequence ,Gene ,HLA-A1 Antigen ,Base Sequence ,Genes, Immunoglobulin ,HLA-A Antigens ,Sequence Homology, Amino Acid ,Nucleic acid sequence ,Antibodies, Monoclonal ,RNA-Directed DNA Polymerase ,General Medicine ,Molecular biology ,Immunoglobulin Light Chains ,Immunoglobulin Heavy Chains ,Sequence Alignment - Abstract
Nucleotide sequences of the heavy and light chain variable (VH and VL) regions of a human monoclonal antibody (4-35-7), which recognized HLA-A1, A23 and A24, were determined by means of the reverse transcriptase-polymerase chain reaction. This antibody was generated by Epstein-Barr virus transformation of lymphocytes obtained from a multiparous donor, followed by fusion with mouse myeloma cells. The VH gene segment belonged to the VHIII gene family, and used the DXP4 and JH4 gene segments. This VH gene segment had 92.9% homology to the germline gene VH26, and contained 21 nucleotide substitutions. Fourteen of them generated the replacements of amino acids, while 7 failed to generate the replacement. The ratio of replacement to silent mutations in complementarity determining regions (CDRs) was 7.0. The VL gene segment belonged to the VkI gene family, and used Jk4. This VL gene segment showed 96.1% homology to the germline gene HK102, and contained 11 nucleotide substitutions. Seven of them generated the replacement of amino acids, while 4 failed to generate the replacement. The high ratio of replacement to silent mutations in CDRs of the VH gene segment suggested that the multiparity caused the processes of antigenic selection and somatic mutation, and generated this anti-HLA antibody.
- Published
- 1993
23. A human monoclonal antibody that detects HLA-A1, A23 and A24 antigens
- Author
-
T. Kurachi, Ryuzo Ohno, K. Kubo, J. Tachino, Tomoki Naoe, H. Yamaguchi, and K. Ueda
- Subjects
medicine.drug_class ,Immunology ,HLA-A24 Antigen ,Enzyme-Linked Immunosorbent Assay ,Human leukocyte antigen ,Monoclonal antibody ,Biochemistry ,Epitope ,Cell Fusion ,Mice ,Antigen ,Tumor Cells, Cultured ,Genetics ,medicine ,Animals ,Humans ,Immunology and Allergy ,Cloning, Molecular ,Cells, Cultured ,HLA-A1 Antigen ,B-Lymphocytes ,Hybridomas ,HLA-A Antigens ,biology ,Immune adherence ,Antibodies, Monoclonal ,General Medicine ,Flow Cytometry ,Virology ,Molecular biology ,Blotting, Southern ,Titer ,Subcloning ,biology.protein ,Female ,Antibody ,Multiple Myeloma - Abstract
We report the production and characterization of a human monoclonal IgM (mu, kappa) antibody recognizing the HLA A1, A23 and A24 antigens. B lymphocytes obtained from a multiparous Japanese woman were transformed in vitro by Epstein-Barr virus, screened with an immune adherence assay, and fused with a murine myeloma cell line, P3-X63-Ag8.653. After subcloning by limiting dilution three times, a stable antibody-secreting hybridoma cell line, 4-35-7, was identified. The culture supernant had a titer of 1:32-64 against each of A1-, A23- and A24-positive lymphocyte panels, and showed complete correlation (r = 1.00) with the A1, A23 and A24 antigens on a lymphocyte panel of 287 unrelated, class I HLA-typed donors by the NIH cytotoxicity assay. Monoclonality of the antibody was ensured by Southern blot analysis of the human immunoglobulin heavy chain gene of 4-35-7. In view of the published data on HLA class I nucleotide sequences, the antibody may recognize an antigeneic determinant including two amino acid residues, Asp-166 and Gly-167, in the alpha 2 helix of the class I molecule that are specific for A1, A23 and A24 so far analyzed.
- Published
- 1993
24. Conformational changes within the HLA-A1:MAGE-A1 complex induced by binding of a recombinant antibody fragment with TCR-like specificity
- Author
-
Barbara Uchanska-Ziegler, Andreas Ziegler, Ardeschir Vahedi-Faridi, Wolfram Saenger, and Pravin Kumar
- Subjects
CD74 ,Protein Conformation ,Recombinant Fusion Proteins ,Receptors, Antigen, T-Cell ,chemical and pharmacologic phenomena ,Human leukocyte antigen ,Crystallography, X-Ray ,Ligands ,Major histocompatibility complex ,Biochemistry ,Article ,Protein structure ,Antigens, Neoplasm ,MHC class I ,Humans ,Molecular Biology ,HLA-A1 Antigen ,biology ,T-cell receptor ,MHC restriction ,Molecular biology ,Neoplasm Proteins ,biology.protein ,Biophysics ,Melanoma-Specific Antigens ,CD8 ,Protein Binding - Abstract
Although there is X-ray crystallographic evidence that the interaction between major histocompatibility complex (MHC, in humans HLA) class I molecules and T cell receptors (TCR) or killer cell Ig-like receptors (KIR) may be accompanied by considerable changes in the conformation of selected residues or even entire loops within TCR or KIR, conformational changes between receptor-bound and -unbound MHC class I molecules of comparable magnitude have not been observed so far. We have previously determined the structure of the MHC class I molecule HLA-A1 bound to a melanoma antigen-encoding gene (MAGE)-A1-derived peptide in complex with a recombinant antibody fragment with TCR-like specificity, Fab-Hyb3. Here, we compare the X-ray structure of HLA-A1:MAGE-A1 with that complexed with Fab-Hyb3 to gain insight into structural changes of the MHC molecule that might be induced by the interaction with the antibody fragment. Apart from the expulsion of several water molecules from the interface, Fab-Hyb3 binding results in major rearrangements (up to 5.5 Å) of heavy chain residues Arg65, Gln72, Arg145, and Lys146. Residue 65 is frequently and residues 72 and 146 are occasionally involved in TCR binding-induced conformational changes, as revealed by a comparison with MHC class I structures in TCR-liganded and -unliganded forms. On the other hand, residue 145 is subject to a reorientation following engagement of HLA-Cw4 and KIR2DL1. Therefore, conformational changes within the HLA-A1:MAGE-A1:Fab-Hyb3 complex include MHC residues that are also involved in reorientations in complexes with natural ligands, pointing to their central importance for the peptide-dependent recognition of MHC molecules.
- Published
- 2008
25. INCREASED INTERLEUKIN-2 RECEPTOR AFFINITY IN NORMAL HLA A1 B8 DR3 SUBJECTS
- Author
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M. Vindimian, G. Pomier, J. C. Le Petit, and J. C. Healy
- Subjects
Adult ,Male ,musculoskeletal diseases ,Interleukin 2 ,medicine.medical_specialty ,endocrine system diseases ,Lymphocyte ,medicine.medical_treatment ,Immunology ,Stimulation ,In Vitro Techniques ,Biology ,Lymphocyte Activation ,HLA-B8 Antigen ,law.invention ,HLA-DR3 Antigen ,HLA Antigens ,immune system diseases ,Cell surface receptor ,law ,Internal medicine ,Immunogenetics ,Genetics ,medicine ,Humans ,skin and connective tissue diseases ,Receptor ,HLA-A1 Antigen ,Lymphoblast ,Receptors, Interleukin-2 ,Middle Aged ,medicine.anatomical_structure ,Cytokine ,Endocrinology ,Recombinant DNA ,Interleukin-2 ,Female ,medicine.drug - Abstract
SUMMARY Twenty-two subjects (11 HLA A1 B8 DR3, 11 non-A1 B8 DR3) were tested for the capacity of their lymphocytes to express Tac molecules and interleukin-2 (IL-2) receptors (quantified using radiolabelled IL-2) after mitogen stimulation. Ten of these subjects (five Al B8 DR3 and five non-A1 B8 DR3) were also tested for the ability of their lymphocytes to proliferate under IL-2 stimulation. Al B8 DR3 subjects express a normal number of high-affinity IL-2 receptor sites, but the affinity of these receptors sites is significantly increased. Unexpectedly, Al B8 DR3 lymphoblasts show a lower response to IL-2 than non-Al B8 DR3 for high doses of recombinant IL-2.
- Published
- 1990
26. IEF ANALYSIS OF HLA MOLECULES IMMUNOPRECIPITATED BY PUTATIVE ANTI-CLASS I-LIKE ALLOANTISERA
- Author
-
Sandra D'Alfonso, Patricia Richiardi, and Tiziana Crepaldi
- Subjects
Antiserum ,Immunoprecipitation ,Immunology ,chemical and pharmacologic phenomena ,Human leukocyte antigen ,Immunogenetics ,Biology ,Lymphocyte Activation ,Precipitin Tests ,Molecular biology ,Epitope ,Epitopes ,Isoelectric point ,HLA Antigens ,Isoantibodies ,HLA-A2 Antigen ,Genetics ,biology.protein ,Humans ,Isoelectric Focusing ,Cell activation ,HLA-A1 Antigen ,Antilymphocyte Serum ,Phytohaemagglutinin - Abstract
SUMMARY Two human alloantisera, previously described as possibly detecting new beta 2-microglobulin associated proteins, selectively expressed on HLA-A2 and HLA-A1 phytohaemagglutinin (PHA)-activated lymphocytes, immunoprecipitated only molecules with the same isoelectric point as HLA-A1 and A2 products. This result suggests that the selected alloantisera do not react with the products of an HLA class I locus different from ABC but probably recognize a new epitope arising on HLA-A molecules upon conformational changes consequent to cell activation.
- Published
- 1990
27. Increased frequency of HLA-A1 in calcifying tendinitis
- Author
-
H. K. Uhthoff, Dharmendra P.S. Sengar, and R. J. McKendry
- Subjects
Shoulder ,medicine.medical_specialty ,Immunology ,MEDLINE ,Immunogenetics ,Biochemistry ,Disease susceptibility ,Gene Frequency ,Tendinitis ,HLA Antigens ,Genetics ,medicine ,Humans ,Immunology and Allergy ,Prospective Studies ,Prospective cohort study ,Allele frequency ,HLA-A1 Antigen ,business.industry ,Calcinosis ,General Medicine ,medicine.disease ,Dermatology ,Tendinopathy ,Calcifying tendinitis ,Disease Susceptibility ,business - Published
- 2008
28. An unlikely rare result of HLA-A*0236, *3601 masking the presence of a novel allele A*0114
- Author
-
Steven T. Cox, John Crowley, Ann-Margaret Little, and C. Dunne
- Subjects
medicine.medical_specialty ,Blood transfusion ,medicine.medical_treatment ,Molecular Sequence Data ,Immunology ,Reference laboratory ,Biology ,Biochemistry ,White People ,Irish ,HLA Antigens ,HLA-A2 Antigen ,Genetics ,medicine ,Humans ,Immunology and Allergy ,Base sequence ,Lymphocytes ,Alleles ,HLA-A1 Antigen ,DNA Primers ,Polymorphism, Genetic ,Base Sequence ,HLA-A Antigens ,General Medicine ,humanities ,language.human_language ,Histocompatibility ,HLA-A ,Family medicine ,language - Abstract
J. Crowley, C. Dunne, S. T. Cox & A.-M. Little 1 National Histocompatibility and Immunogenetics Reference Laboratory, Irish Blood Transfusion Service, National Blood Centre, James’s Street, Dublin 8, Ireland 2 Histocompatibility Laboratories and Research Institute, The Anthony Nolan Trust, The Royal Free Hospital, Pond Street, London NW3 2QG, UK 3 Department of Haematology, The Royal Free Hospital, Pond Street, London NW3 2QG, UK
- Published
- 2007
29. HLA antibody formation within the HLA-A1 crossreactive group in multitransfused platelet recipients
- Author
-
Bruce R. MacPherson
- Subjects
HLA-A Antigens ,biology ,Platelet Count ,Platelet Transfusion ,Hematology ,Histocompatibility Testing ,Human leukocyte antigen ,Cross Reactions ,Virology ,Blood cell ,Platelet transfusion ,medicine.anatomical_structure ,Antigen ,Antibody Specificity ,HLA Antigens ,Antibody Formation ,Immunology ,biology.protein ,medicine ,Humans ,Blood Transfusion ,Platelet ,Hla antibodies ,Antibody ,HLA-A1 Antigen - Abstract
The formation of intragroup antibodies, HLA antibodies directed against antigens in the same crossreactive group (CREG) as those of the serum donor, may be an important cause of transfusion failures in patients receiving HLA-matched platelets. Twenty-two patients whose HLA types included at least one antigen in the HLA-A1 CREG were studied. Of the ten patients who formed HLA antibodies, six produced antibodies that reacted with one or more antigens in the HLA-A1 CREG. Five of 12 patients whose HLA types included HLA-A3 formed antibodies directed against HLA-A1-10-11 or HLA-A1-10. In contrast, only one of ten individuals whose phenotypes included HLA-A1, HLA-A11, or both produced anti-HLA-A3. Eleven incompatible retrospective crossmatches were observed in recipients of HLA-matched platelets attributable to intragroup antibodies. Patients receiving incompatible platelets had unsatisfactory post-transfusion platelet count increments. It is concluded that intragroup antibodies, such as those directed against antigens in the HLA-A1 CREG, are an important cause of platelet transfusion failures in patients requiring long-term platelet transfusion support. These antibodies can be identified by routinely screening recipient sera for HLA antibodies and performing retrospective crossmatches using the lymphocytotoxicity technique.
- Published
- 1989
30. Congenital heart block immunogenetics. Evidence of an additional role of hla class iii antigens and independence of Ro Autoantibodies
- Author
-
Moreno F, Jose L. Vicario, Vazquez-Rodriguez Jj, Jorge Martinez-Laso, Pascual D, Antonio Arnaiz-Villena, and Lavilla P
- Subjects
musculoskeletal diseases ,medicine.medical_specialty ,endocrine system diseases ,Offspring ,Immunology ,Immunogenetics ,Human leukocyte antigen ,HLA-B8 Antigen ,HLA-DR3 Antigen ,Rheumatology ,Antigen ,HLA Antigens ,immune system diseases ,Internal medicine ,medicine ,Humans ,Immunology and Allergy ,Pharmacology (medical) ,skin and connective tissue diseases ,HLA-A1 Antigen ,Autoantibodies ,biology ,business.industry ,Haplotype ,Autoantibody ,Infant ,Heart Block ,Endocrinology ,Haplotypes ,Antibodies, Antinuclear ,biology.protein ,Female ,Antibody ,business ,Anti-SSA/Ro autoantibodies - Abstract
Congenital complete heart block (CCHB) occurs in the offspring of mothers who have the HLA-A1;B8; DR3 haplotype and Ro (SS-A) autoantibodies. It has been shown that the presence of HLA-DR3 in mothers may facilitate Ro synthesis, but may not, by itself, be sufficient to induce CCHB in the offspring. However, maternal DR3 and Ro antibody seem to be independent factors associated with CCHB. Other HLA antigens, including class III (complement) genes, may also be necessary to induce CCHB in newborns since A1;B8; DR3 haplotypes, together with BfS and/or C4AQ0B1, are increased in Ro+ mothers of infants with CCHB compared with both controls and with Ro+ mothers whose offspring do not have CCHB. On the other hand, DR3 genes in a different HLA haplotype (i.e., B18; BfF1;DR3) are nonpathogenetic; this latter finding may be due to a DR3 gene's intrinsic difference or to the influence of neighboring genes. Also, a trend toward DR3 bias transmission is observed in DR3+ mothers who are also Ro+; fetal DR3 might protect the fetus against in utero death when Ro antibodies are present.
- Published
- 1989
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