Using PCR with sequence-specific primers (SSP) and subsequent sequencing of exons 2 and 3, we identified an example of B*15:33 in a likely north-western European Caucasoid volunteer haemopoietic stem cell (HSC) donor. This was only the second example submitted to the IMGT/HLA database since B*15:33 was first described in 1996. B*15:33 differs from B*15:01:01:01 by three nucleotides resulting in two amino acid differences with B*15:01 (131S>R, 138T>K). This allele encodes a typical HLA-B62 specificity--as confirmed using 17 local antisera from parous women and 19 monoclonal antibodies directed towards B15, B62 and B63 specificities. Importantly, it also reacted as a Cw5/Cw8 specificity when tested against 21 Cw5, Cw5/Cw8 and Cw8 antisera. This Cw5/Cw8 reactivity is probably due to the B*15:33 specificity having lysine at position 138 which is possessed by numerous C*05 and many C*08 products. B*15:33 is likely to have derived from a HLA-B/C inter-locus gene conversion event. HLA-B*15:33 is clearly rare--this single example was found during the HLA PCR-SSP-based typing of 57,079 potential HSC donors. This indicates an allele frequency of <0.00001 in blood donors resident in Wales. An Epstein-Barr virus transformed B-cell line from the HLA-B*15:33 donor is available.
The sequencing of exons 2-7 of a likely new HLA-C*05 allele identified the second example of HLA-C*05:142, in a male UK European, within a few months of the first example being found in Germany. C*05:142 differs from C*05:01:01:01 by a single base (395G>C) in exon 3 resulting in an amino acid substitution of R108P. Comprehensive serological HLA-Cw5 typing, using 19 antisera, indicated that C*05:142 encodes a "normal" Cw5 specificity. Failure to identify the involvement of position 108 in published HLA-C epitopes supported this assertion. The likely HLA class I C*05:142-bearing haplotype is A*02:01~C*05:142~B*44:02. This new allele has a maximum frequency of 0.00001, in 34,743 sequenced-based typed subjects, contrasting with that of C*05:01 (allele frequency 0.10441), in our local, largely UK European, blood donors.
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