Identification of the gene encoding a novel HLA-B39 subtype Two amino acid substitutions on the β-sheet out of the peptide-binding floor form a novel serological epitope

Abstract Serologic analysis suggests the existence of a novel HLA-B39 subtype (HLA-B39N) in the Japanese population. To identify this novel allele, a gene encoding HLA-B39N was cloned and the exons were sequenced. A gene encoding HLA-B39N (B ∗ 3904) and B ∗ 39011 differs by two nucleotide substitutions at codons 11 and 12 whereas B ∗ 3904 and B ∗ 39013 differ by three nucleotide substitutions at codons 11, 12, and 312. One nucleotide difference at codon 11 produces a change from serine in B ∗ 3901 to alanine in B ∗ 3904 whereas another difference at codon 12 changes valine in B ∗ 3901 to methionine in B ∗ 3904. The residues 11 and 12 are located on the β-sheet out of the peptide-binding floor and are completely buried in the molecule. These results suggest that the substitutions at these residues alter the conformation of other residues forming epitopes of alloantibodies. Analysis of HLA-B ∗ 3901 genes in the Japanese population showed that both B ∗ 39011 and B ∗ 39013 were observed in the Japanese population. The present study suggests that B ∗ 3904 may have evolved from B ∗ 39011 rather than B ∗ 39013.