Effect of the substitutions in the alpha helix and the beta sheet of HLA class I molecule on allorecognition of T cells specific for HLA-B51 and HLA-Bw53.

HLA-B51 and HLA-Bw53 differ by eight amino acids on the alpha 2 domain. Of these eight amino acid substitutions, two are in the alpha helix and six are in the beta sheet. The effect of these substitutions on allorecognition of HLA-B51-specific cytotoxic T lymphocyte (CTL) clones and HLA-Bw53-specific CTL clones was investigated using chimeric antigen (Ag) between HLA-B51 and HLA-Bw53. Of 12 HLA-B51-specific CTL clones, recognition of one clone was abolished by the substitutions on the beta sheet alone, that of two clones by the substitutions on the alpha helix alone, and that of nine clones not only by the substitutions on the alpha helix but also by those on the beta sheets. On the other hand, of 17 HLA-Bw53-specific CTL clones, recognition of 10 clones was affected by the substitutions on the alpha helix alone and that of 7 clones not only by the substitutions on the alpha helix but also by those on the beta sheet. The present study demonstrated that the substitutions (residues 152 and 171) on the alpha helix critically affect recognition of HLA-B51-specific CTL clones and HLA-Bw53-specific CTL clones and that the substitutions on the beta sheet affect also recognition of the majority of HLA-B51-specific CTL clones and 40% of HLA-Bw53-specific CTL clones. These results indicate that the substitutions at the floor of the peptide binding groove affect recognition of allogeneic CTL.