Roles of the six peptide-binding pockets of the HLA-A2 molecule in allorecognition by human cytotoxic T-cell clones.
To evaluate the contribution of the major histocompatibility complex class I pockets to the binding of self-peptides recognized by alloreactive cytotoxic T-lymphocyte (CTL) clones, we have constructed an extensive library of HLA-A2 mutants with different amino acid substitutions in each of the six pockets. When these mutants were tested in cytotoxicity assays with a panel of HLA-A2-specific alloreactive CTL clones, each CTL clone showed a unique pattern of reactivity, implying the different contributions of each pocket to binding individual peptides. We noted that the majority of the mutants in pocket B significantly affect recognition by the CTL clones. Unexpectedly, the mutations influencing allorecognition are found in all other pockets as well. Overall, this study demonstrates that each of the six peptide-binding pockets plays an important and distinct role in binding of self-peptides required for recognition of the HLA-A2 molecule by alloreactive CTLs.
Matsui
M
M
Department of Microbiology and Immunology, University of North Carolina, Chapel Hill 27599.
Hioe
C E
CE
Frelinger
J A
JA
D016923:Cell Death / Q000276:immunology; D002999:Clone Cells; D003602:Cytotoxicity, Immunologic; D004252:DNA Mutational Analysis; D000939:Epitopes; D005802:Genes, MHC Class II / Q000235:genetics*; D015789:HLA-A2 Antigen / Q000235:genetics / Q000276:immunology*; D006648:Histocompatibility / Q000276:immunology*; D006801:Humans; D010455:Peptides / Q000378:metabolism; D013329:Structure-Activity Relationship; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000939:Epitopes; D015789:HLA-A2 Antigen; D010455:Peptides