Significance of the six peptide-binding pockets of HLA-A2.1 in influenza A matrix peptide-specific cytotoxic T-lymphocyte reactivity.

To evaluate the roles of the six peptide-binding pockets of HLA-A2.1 in FMP-specific CTL recognition, we have constructed an extensive library of HMy2.C1R cell lines expressing mutant HLA-A2.1 molecules with different amino acid substitutions in each of the six pockets. These cell lines were tested for their ability to present synthetic FMP 58-66 to FMP-specific, HLA-A2.1-restricted human CTL lines. Six of 12 mutants with amino acid changes in pocket B significantly affect the FMP-specific CTL recognition, suggesting that pocket B plays a critical role in FMP-specific CTL recognition. Surprisingly, mutations in all other pockets, except for pocket F, also have significant effects on the CTL recognition. These results suggest that even the shallow pockets, which are likely to be less critical for peptide binding than the deep pockets, play a crucial role in FMP-specific CTL recognition.