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. 1993 Jan 15;90(2):674–678. doi: 10.1073/pnas.90.2.674

Roles of the six peptide-binding pockets of the HLA-A2 molecule in allorecognition by human cytotoxic T-cell clones.

M Matsui 1, C E Hioe 1, J A Frelinger 1
PMCID: PMC45726  PMID: 7678462

Abstract

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.

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Selected References

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