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

Abstract HLA-B51 and HLA-Bw53 differ by eight amino acids on the α 2 domain. Of these eight amino acid substitutions, two are in the α helix and six are in the of HLA-B51-specific cytotoxic T lympocyte (CTL) β sheet. The effect of these substitutions on allorecognition 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 β sheet alone, that of two clones by the substitutions on the α helix alone, and that of nine clones not only by the substitutions on the α helix but also by those on the β sheets. On the other hand, of 17 HLA-Bw53-specific CTL clones, recognition of 10 clones was affected by the substitutions on the α helix alone and that of 7 clones not only by the substitutions on the α helix but also by those on the β sheet. The present study demonstrated that the substitutions (residues 152 and 171) on the α helix critically affect recognition of HLA-B51-specific CTL clones and HLA-Bw53-specific CTL clones and that the substitutions on the β 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 allogeniic CTL. Human Immunology 33, 82–88 (1992)