Effect of single amino acid substitution at residue 167 of HLA-B51 on binding of antibodies and recognition of T cells.

We recently showed that a single amino acid substitution of tryptophane into glycine at residue 167 facing the "A pocket" forms a novel HLA-B51 subtype, B5103, which is serologically discriminated as HLA-BTA. CDC assay of human alloantisera specific for the HLA-B5 CREG against B5103- or B5101-transfected human B-cell line, Hmy2C1R (C1R), supported the belief that human alloantisera can discriminate B5103 from B5101 Ag. Moreover, we found that 4D12 anti-B5, B35 CREG mAb cannot bind to B5103 Ag on C1R cells or L cells although it binds to B5101 Ag on both cells. These results indicate that alloantibodies can detect a single amino acid substitution at residue 167. Furthermore, it was suggested that 4D12 mAb recognizes the structure formed by the HLA-peptide complex since this mAb did not bind to empty HLA-B5, B35 CREG Ag on RMA-S transfectants. Six of eight anti-HLA-B5101 CTL clones are not able to kill C1R cells expressing B5103, indicating that conformational change of the A pocket by substitution at residue 167 has a crucial influence on recognition of alloreactive T cells. Therefore, discrimination of B5103 from B*5101 would seem to be important in bone marrow transplantation.