The role of the conserved residue in pocket A and the polymorphic residue in pocket E of HLA-B*3501 in presentation of human minor histocompatibility peptides to T cells.
We investigated T cell recognition for human minor histocompatibility (hmH) peptides using HLA-B*3501 restricted, hmH specific cytotoxic T lymphocytes (CTL) clones. These CTL clones killed C1R cells expressing HLA-B*3501 but not C1R cells expressing chimeric antigens between HLA-B*3501 and HLA-B*5101. They also failed to kill C1R cells expressing HLA-B*3501 mutants at residue 152 (B*3501-V152E) or at residue 171 (B*3501-Y171H). The CTL clone failed to kill C1R cells expressing these mutant molecules loaded with the hmH peptides isolated from C1R-B*3501 cells although it killed a self-B cell line expressing HLA-B3501 loaded with the specific hmH peptides. The CTL clone also failed to kill T2 cells expressing the mutant molecules loaded with the specific peptides whereas it killed T2 cells expressing HLA-B*3501 loaded with the specific peptide. On the other hand, naturally occurring specific hmH peptides were isolated from purified B*3501-V152E and B*3501-Y171H molecules, indicating that both HLA-B*3501-V152E and HLA-B*3501-Y171H molecules can bind the hmH peptides. These findings indicate that both the conserved residue 171 in pocket A and the polymorphic residue 152 in pocket E are critical in recognition of the T cells but not binding of the hmH peptides. Furthermore, these results provide the possibility that the TCR recognizes a conformational structure of hmH peptides bound to HLA-B*3501 molecules.
Takiguchi
M
M
Department of Tumor Biology and Immunology, University of Tokyo, Japan.
Kawaguchi
G
G
Sekimata
M
M
Hiraiwa
M
M
Kariyone
A
A
Takamiya
Y
Y
D017951:Antigen Presentation / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D002999:Clone Cells; D003602:Cytotoxicity, Immunologic; D005434:Flow Cytometry; D015797:HLA-B35 Antigen / Q000235:genetics / Q000276:immunology*; D006801:Humans; D015778:Minor Histocompatibility Antigens / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014162:Transfection
D015797:HLA-B35 Antigen; D015778:Minor Histocompatibility Antigens