Structural analysis of HLA-B40 epitopes.

Two genes encoding HLA-B60 or HLA-B61 were cloned from Japanese and the exons of their genes were sequenced. One silent mutation was observed at the exon 1 between HLA-B60 (B40012) and B40011. Seven nucleotide substitutions were seen at the exon 3 between HLA-B61 (B4006) and B4002. Three substitutions at codon 95, CTC in B4002 to TGG in B4006, changed Leu in B4002 to Trp in B4006, while two substitutions at codon 97, AGC in B4002 and ACG in B4006, changed Ser in B4002 to Thr in B4006. Since B4002 shares the epitope of alloantibodies specific for HLA-B61, two HLA-B61 subtypes are discriminated by two amino acid substitutions at residues 95 and 97. B40012 and B*4006 differ by four amino acid substitutions on the beta sheet and five amino acid substitutions on the alpha 2 helix. Since the residues at the beta sheet seem hardly to affect the binding of alloantibody, it is suspected that the residues on the alpha 2 helix provide epitopes for alloantibodies that discriminate allospecificity between HLA-B60 and HLA-B61.