Role of HLA-B*5101 binding nonamer peptides in formation of the HLA-Bw4 public epitope.

HLA-Bw4 is one of two HLA-B public epitopes which are discriminated by specific alloantisera and mAb. It is believed that the 77-83 of HLA-B molecules form the Bw4 epitope recognized by specific antibodies. This epitope is also recognized by NKB1 receptors on NK cells. We investigated the role of a peptide bound to HLA-B molecules on the formation of the Bw4 epitope recognized by two HLA-Bw4-specific mAb, TU109 and TU48, which recognized the difference of the Bw4 epitope among HLA-B52, -B52 and -B53. Recognition of the HLA-B*5101-peptide complex by these mAb was examined using a panel of HLA-B*5101 binding nonamer peptides. The sequence of HLA-B*5101 binding peptides has a minimum influence on the binding of TU48 mAb to HLA-B*5101 molecules. In contrast, the binding of TU109 mAb to HLA-B*5101 molecules was critically influenced by the sequence of a peptide bound to HLA-B*5101 molecules. TU109 mAb did not recognize HLA-B*5101 binding peptides carrying small or negatively charged residues at P8. The results were confirmed by a panel of mutant peptides at P8. Taken together, these results indicate that a positively charged or neutralized side chain of P8 is critical for the epitope formation of Bw4 recognized by this mAb.