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

Serological 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 (B3904) and B39011 differs by two nucleotide substitutions at codons 11 and 12 whereas B3904 and B39013 differ by three nucleotide substitutions at codons 11, 12, and 312. One nucleotide difference at codon 11 produces a change from serine in B3901 to alanine in B3904 whereas another difference at codon 12 changes valine in B3901 to methionine in B3904. The residues 11 and 12 are located on the beta-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-B3901 genes in the Japanese population showed that both B39011 and B39013 were observed in the Japanese population. The present study suggests that B3904 may have evolved from B39011 rather than B39013.