A novel HLA-B*40 sequence - B*40:92

P>A new allele, HLA-B*40:92, was identified in a north-western European subject during polymerase chain reaction using sequence-specific priming (PCR-SSP)-based typing of haematopoietic stem cell (HSC) donors. B*40:92 differs from B*40:01:01 by six nucleotides at positions 559, 560, 603, 605, 610 and 618 in exon 3 which represents a substitution motif of at least 60 nucleotides. This motif, which occurs in numerous HLA alleles including the relatively high frequency B*15 and B*35 allele families, encode four amino acid changes at positions 163 (glutamic acid > leucine), 177 (aspartic acid > glutamic acid), 178 (lysine > threonine), 180 (glutamic acid > glutamine) and a silent substitution, conserved alanine, at codon 182. Thus, it is likely that HLA-B*40:92 occurred following a gene conversion-like or interallelic recombination event involving B*40:01:01 and probably a B*15 or more likely a B*35 family allele. HLA-B*40:92 was found on a haplotype with HLA-A*02:01, B*40:92, C*03:04, DRB1*13:02, DRB3*03:01, DQA1*01:02, DQB1*06:04, DPA1*02:02, DPB1*05:01. Tests on 69 selected B40 and B35 antisera and Lambda Monoclonal Trays (TM) show that B*40:92 encodes a 'short' B40/B60 serological specificity which displays some HLA-B35 reactivity. The HLA-B40 and HLA-B35 motifs (possible epitopes) responsible for this serological reactivity were identified. This single example of HLA- B*40:92 was found in 56,823 consecutive HLA PCR-SSP typed HSC donors indicating a carriage frequency of 0.00176% (allele frequency 0.00001) in blood donors resident in Wales. An Epstein-Barr virus transformed B-cell line from the HLA-B*40:92 donor is available.