Structural analysis of HLA-B40 epitopes

Abstract 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 (B ∗ 40012) and B ∗ 40011. Seven nucleotide substitutions were seen at the exon 3 between HLA-B61 (B ∗ 4006) and B ∗ 4002. Three substitutions at codon 95, CTC in B ∗ 4002 to TGG in B ∗ 4006, changed Leu in B ∗ 4002 to Trp in B ∗ 4006, while two substitutions at codon 97, AGC in B ∗ 4002 and ACG in B ∗ 4006, changed Ser in B ∗ 4002 to Thr in B ∗ 4006. Since B ∗ 4002 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. B ∗ 40012 and B ∗ 4006 differ by four amino acid substitutions on the β sheet and five amino acid substitutions on the α 2 helix. Since the residues at the β sheet seem hardly to affect the binding of alloantibody, it is suspected that the residues on the α 2 helix provide epitopes for alloantibodies that discriminate allospecificity between HLA-B60 and HLA-B61.