6 results on '"HLA-A1 Antigen"'
Search Results
2. Immune monitoring with iTAg MHC Tetramers for prediction of recurrent or persistent cytomegalovirus infection or disease in allogeneic hematopoietic stem cell transplant recipients: a prospective multicenter study.
- Author
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Gratama JW, Boeckh M, Nakamura R, Cornelissen JJ, Brooimans RA, Zaia JA, Forman SJ, Gaal K, Bray KR, Gasior GH, Boyce CS, Sullivan LA, and Southwick PC
- Subjects
- Adolescent, Adult, Aged, CD4-Positive T-Lymphocytes cytology, CD4-Positive T-Lymphocytes immunology, Cytomegalovirus Infections diagnosis, Cytomegalovirus Infections etiology, Female, Flow Cytometry, HLA-A Antigens genetics, HLA-A Antigens immunology, HLA-A1 Antigen, HLA-B Antigens genetics, HLA-B Antigens immunology, HLA-B7 Antigen, Hematopoietic Stem Cell Transplantation adverse effects, Histocompatibility Testing, Humans, Longitudinal Studies, Male, Middle Aged, Postoperative Complications diagnosis, Postoperative Complications etiology, Prognosis, Prospective Studies, Reproducibility of Results, Transplantation, Homologous, Young Adult, Cytomegalovirus Infections immunology, Hematopoietic Stem Cell Transplantation methods, Monitoring, Immunologic methods, Postoperative Complications immunology
- Abstract
Cytomegalovirus (CMV) infection is an important cause of morbidity and mortality in hematopoietic stem cell transplant recipients despite the introduction of posttransplantation viral monitoring and preemptive antiviral therapy. We evaluated the use of HLA class I tetramers in monitoring CMV-specific T-cell recovery to predict patients at risk for CMV-related complications. This prospective multicenter clinical trial obtained nearly 1400 tetramer/allele results in more than 800 biweekly blood samples from 83 patients monitored for 1 year after transplantation. Major HLA types were included (A*0101, A*0201, B*0702, B*0801, B*3501). iTAg MHC Tetramers (Beckman Coulter) were used to enumerate CMV-specific CD8(+) T cells by flow cytometry using a single-platform absolute counting method. Assay variability was 8% or less and results were available within 3 hours. Delayed recovery of CMV-specific T cells (< 7 cells/μL in all blood samples during the first 65 days after transplantation) was found to be a significant risk factor for CMV-related complications; these patients were more likely to develop recurrent or persistent CMV infection (relative risk 2.6, CI 1.2-5.8, P = .01) than patients showing rapid recovery, which was associated with protection from CMV-related complications (P = .004). CMV tetramer-based immune monitoring, in conjunction with virologic monitoring, can be an important new tool to assess risk of CMV-related complications and to guide preemptive therapeutic choices.
- Published
- 2010
- Full Text
- View/download PDF
3. HLA-A*02 is associated with a reduced risk and HLA-A*01 with an increased risk of developing EBV+ Hodgkin lymphoma.
- Author
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Niens M, Jarrett RF, Hepkema B, Nolte IM, Diepstra A, Platteel M, Kouprie N, Delury CP, Gallagher A, Visser L, Poppema S, te Meerman GJ, and van den Berg A
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Epstein-Barr Virus Infections complications, Female, Genetic Predisposition to Disease, HLA-A1 Antigen, HLA-A2 Antigen, Haplotypes, Hodgkin Disease complications, Hodgkin Disease virology, Humans, Male, Middle Aged, Polymorphism, Single Nucleotide, Risk Factors, Epstein-Barr Virus Infections genetics, HLA-A Antigens genetics, Hodgkin Disease genetics
- Abstract
Previous studies showed that the HLA class I region is associated with Epstein-Barr virus (EBV)-positive Hodgkin lymphoma (HL) and that HLA-A is the most likely candidate gene in this region. This suggests that antigenic presentation of EBV-derived peptides in the context of HLA-A is involved in the pathogenesis of EBV+ HL by precluding efficient immune responses. We genotyped exons 2 and 3, encoding the peptide-binding groove of HLA-A, for 32 single nucleotide polymorphisms in 70 patients with EBV+ HL, 31 patients with EBV- HL, and 59 control participants. HLA-A*01 was significantly overrepresented and HLA-A*02 was significantly underrepresented in patients with EBV+ HL versus controls and patients with EBV- HL. In addition, HLA-A*02 status was determined by immunohistochemistry or HLA-A*02-specific polymerase chain reaction (PCR) on 152 patients with EBV+ HL and 322 patients with EBV- HL. The percentage of HLA-A*02+ patients in the EBV+ HL group (35.5%) was significantly lower than in 6107 general control participants (53.0%) and the EBV- HL group (50.9%). Our results indicate that individuals carrying the HLA-A*02 allele have a reduced risk of developing EBV+ HL, while individuals carrying the HLA-A*01 allele have an increased risk. It is known that HLA-A*02 can present EBV-derived peptides and can evoke an effective immune response, which may explain the protective phenotype.
- Published
- 2007
- Full Text
- View/download PDF
4. A neoepitope generated by an FLT3 internal tandem duplication (FLT3-ITD) is recognized by leukemia-reactive autologous CD8+ T cells.
- Author
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Graf C, Heidel F, Tenzer S, Radsak MP, Solem FK, Britten CM, Huber C, Fischer T, and Wölfel T
- Subjects
- Amino Acid Sequence, Antigen Presentation, Cell Line, Cell Line, Tumor, Epitopes genetics, HLA-A Antigens genetics, HLA-A Antigens metabolism, HLA-A1 Antigen, Humans, In Vitro Techniques, Leukemia, Myeloid, Acute enzymology, Molecular Sequence Data, RNA, Messenger genetics, Transfection, CD8-Positive T-Lymphocytes immunology, Gene Duplication, Leukemia, Myeloid, Acute genetics, Leukemia, Myeloid, Acute immunology, fms-Like Tyrosine Kinase 3 genetics, fms-Like Tyrosine Kinase 3 immunology
- Abstract
The FLT3 receptor tyrosine kinase is expressed in more than 90% of acute myelogeneous leukemias (AMLs), up to 30% of which carry an internal tandem duplication (ITD) within the FLT3 gene. Although varying duplication sites exist, most FLT3-ITDs affect a single protein domain. We analyzed the FLT3-ITD of an AML patient for encoding HLA class I-restricted immunogenic peptides. One of the tested peptides (YVDFREYEYY) induced in vitro autologous T-cell responses restricted by HLA-A*0101 that were also detectable ex vivo. These peptide-reactive T cells recognized targets transfected with the patient's FLT3-ITD, but not wild-type FLT3, and recognized the patient's AML cells. Our results demonstrate that AML leukemic blasts can in principle process and present immunogenic FLT3-ITD neoepitopes. Therefore, FLT3-ITD represents a potential candidate target antigen for the immunotherapy of AML.
- Published
- 2007
- Full Text
- View/download PDF
5. The minor histocompatibility antigen HA-3 arises from differential proteasome-mediated cleavage of the lymphoid blast crisis (Lbc) oncoprotein.
- Author
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Spierings E, Brickner AG, Caldwell JA, Zegveld S, Tatsis N, Blokland E, Pool J, Pierce RA, Mollah S, Shabanowitz J, Eisenlohr LC, van Veelen P, Ossendorp F, Hunt DF, Goulmy E, and Engelhard VH
- Subjects
- A Kinase Anchor Proteins, ATP Binding Cassette Transporter, Subfamily B, Member 2, ATP-Binding Cassette Transporters metabolism, Acute Disease, Adaptor Proteins, Signal Transducing, Alleles, Amino Acid Sequence, Amino Acid Substitution, Antigen Presentation, CD8-Positive T-Lymphocytes immunology, Clone Cells immunology, Epitopes, T-Lymphocyte immunology, Epitopes, T-Lymphocyte metabolism, Female, Genotype, HLA-A1 Antigen metabolism, Humans, Leukemia, Myeloid immunology, Leukemia, Myeloid therapy, Male, Minor Histocompatibility Antigens, Molecular Sequence Data, Pedigree, Peripheral Blood Stem Cell Transplantation, Polymorphism, Genetic, Proteasome Endopeptidase Complex, Protein Isoforms genetics, Protein Isoforms metabolism, Proto-Oncogene Proteins metabolism, Sequence Alignment, Sequence Homology, Amino Acid, Cysteine Endopeptidases metabolism, Epitopes, T-Lymphocyte genetics, Multienzyme Complexes metabolism, Protein Processing, Post-Translational, Proto-Oncogene Proteins genetics
- Abstract
Minor histocompatibility (H) antigens crucially affect the outcome of human leukocyte antigen (HLA)-identical allogeneic stem cell transplantation (SCT). To understand the basis of alloimmune responses against minor H antigens, identification of minor H peptides and their antigenicity-determining mechanisms is essential. Here we report the identification of HA-3 and its encoding gene. The HA-3 peptide, VTEPGTAQY (HA-3T), is encoded by the lymphoid blast crisis (Lbc) oncogene. We thus show for the first time that a leukemia-associated oncogene can give rise to immunogenic T-cell epitopes that may have participated in antihost and antileukemic alloimmune responses. Genotypic analysis of HA-3- individuals revealed the allelic counterpart VMEPGTAQY (HA-3M). Despite the lack of T-cell recognition of HA-3- cells, the Thr-->Met substitution had only a modest effect on peptide binding to HLA-A1 and a minimal impact on recognition by T cells when added exogenously to target cells. This substitution did not influence transporter associated with antigen processing (TAP) transport, but, in contrast to the HA-3T peptide, HA-3M is destroyed by proteasome-mediated digestion. Thus, the immunogenicity of minor H antigens can result from proteasome-mediated destruction of the negative allelic peptide.
- Published
- 2003
- Full Text
- View/download PDF
6. DFFRY codes for a new human male-specific minor transplantation antigen involved in bone marrow graft rejection.
- Author
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Vogt MH, de Paus RA, Voogt PJ, Willemze R, and Falkenburg JH
- Subjects
- Amino Acid Sequence, Epitopes immunology, Female, Graft Rejection genetics, H-Y Antigen genetics, HLA-A1 Antigen immunology, HeLa Cells, Histocompatibility Antigens genetics, Humans, Leukemia, Myeloid genetics, Leukemia, Myeloid immunology, Leukemia, Myeloid therapy, Male, Molecular Sequence Data, Peptide Fragments immunology, T-Lymphocytes, Cytotoxic immunology, Transfection, Bone Marrow Transplantation immunology, Graft Rejection immunology, H-Y Antigen immunology, Histocompatibility Antigens immunology
- Abstract
Graft rejection after histocompatibility locus antigen (HLA)-identical stem cell transplantation results from the recognition of minor histocompatibility antigens on donor stem cells by immunocompetent T lymphocytes of recipient origin. T-lymphocyte clones that specifically recognize H-Y epitopes on male target cells have been generated during graft rejection after sex-mismatched transplantation. Previously, 2 human H-Y epitopes derived from the same SMCY gene have been identified that were involved in bone marrow graft rejection. We report the identification of a new male-specific transplantation antigen encoded by the Y-chromosome-specific gene DFFRY. The DFFRY-derived peptide was recognized by an HLA-A1 restricted CTL clone, generated during graft rejection from a female patient with acute myeloid leukemia who rejected HLA-phenotypically identical bone marrow from her father. The identification of this gene demonstrates that at least 2 genes present on the human Y-chromosome code for male-specific transplantation antigens.
- Published
- 2000
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