A novelHLA‐B*14 allele – B*14:53 – genetics and serology

Abstract

HLA-B*14:53 was found in a UK European normal blood donor prior to registration on the Welsh Bone Marrow Donor Registry. It differs from B*14:13 by one base (103G>T) in exon 2 resulting in a substitution of alanine (A) in B*14:13 to serine (S) in B*14:53. Unique among current HLA-B*14 alleles, B*14:53 and B*14:13 share a motif of 59 bases between positions 361 and 419 in exon 3. This motif is present in numerous HLA-B alleles the commonest overall being B*08:01, suggesting that both B*14:53 and B*14:13 arose from intralocus gene conversion events with B*08:01. Thus, B*14:53 probably arose from B*14:01:01 (which has TCC at codon 11 (S), while B*14:13 arose from B*14:02:01:01 which has GCC at codon 11 (A). Additionally, the two likely B*14:53-bearing and B*14:13-bearing haplotypes are typical of B*14:01:01-bearing and B*14:02:01:01-bearing haplotypes, respectively. Serological testing, using 49 antisera with HLA-B64, or B64, B65 reactivity, showed that the B*14:53 specificity did not react as a B64 (B*14:01) specificity and may appear as a short/weak HLA-B14. This implies that residues additional to S at position 11 are involved in HLA-B64 serological identity; for example, the motif 11S 97W 116F is possessed by B*14:01 and many other B*14 products (and B*39:79 plus some HLA-C products) but not B65 (B*14:02) or the B*14:53 specificity. B*14:53 was found in a random HLA sequence-based typed population of 32 530 normal subjects indicating a low precision allele frequency of 0.000015 in subjects resident in Wales.

Epitopes and motifs of theHLA‐B*14 allele family products and relatedHLA‐B14 cross‐reactive specificities

“…Serological HLA typing of our B*14:08:01 donor [and the B*14:53 subject (Street et al., )] gave the expected reactions and specificities applicable to their DNA‐based type (B*14:08:01—A2, A68; “weak/short” B14, B44, Bw4, Bw6; Cw7, Cw‐ [Cw8 not tested] and B*14:53—A2, A32; “weak/short” B14, B44, Bw4, Bw6; Cw5, Cw‐ [Cw8 not tested]) with the exception of that for HLA‐B14 which was unusually weak with some HLA‐B14 antisera and failed to react with others. Importantly, the reactions of both B*14 cells with the five Bw6 antisera and monoclonal antibodies used were as expected for the HLA‐B14 antigen.…”

“…The observations on B*14:08 also generally apply to the B*14:53 product (which has 11S but 97S). Also, B*14:53 has a similar serological reaction pattern to B*14:08:01 cells (Tables and ) and thus reacts as a “short” B14, non‐B64/B64 (Street et al., ).…”

“…The confirmatory sequence was accepted by the WHO Nomenclature Committee in May 2013 (Marsh, ) (cell identification 56468, accession number HF937221). HLA‐B*14:53 cells (HLA Class I type—A*02:01, A*32:01; B*14:53, B*44:02; C*05:01, C*08:02) were from donor 73297 (Street et al., ).…”

“…Epitopes and motifs were assigned to the products of HLA‐B*14 alleles with serological information available from The HLA Dictionary 2008 (Holdsworth et al., ), i.e. B*14:01 to B*14:06, B*14:08 from this current study, and B*14:53 (Street et al., ). Amino acid alignments of these eight products are shown in Figure .…”

“…The B*14:53 specificity differs from B64 by three residues (W97S, Y113H and F116Y). Further, the B*14:53 specificity appears to be neither B64 nor B65 and may behave as a “short” HLA‐B14 specificity (Street, Davies, & Darke, ).…”