Back to Search
Start Over
The minor histocompatibility antigen HA-3 arises from differential proteasome-mediated cleavage of the lymphoid blast crisis (Lbc) oncoprotein.
- Source :
-
Blood [Blood] 2003 Jul 15; Vol. 102 (2), pp. 621-9. Date of Electronic Publication: 2003 Mar 27. - Publication Year :
- 2003
-
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.
- 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
Subjects
Details
- Language :
- English
- ISSN :
- 0006-4971
- Volume :
- 102
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Blood
- Publication Type :
- Academic Journal
- Accession number :
- 12663445
- Full Text :
- https://doi.org/10.1182/blood-2003-01-0260