A novel HLA-B*39 allele (HLA-B*3916) due to a rare mutation causing cryptic splice site activation

A novel HLA-B*39 variant, found in an African patient with sickle cell anem ia undergoing bone marrow transplantation is described. Initially suspected by inconsistent serological typing (B-blank, Bw6), then recognized by PCR- SSP, and finally characterized by nucleotide sequencing, this novel allele is designated HLA-B*3916. It differs from HLA-B*3910 by a point mutation (G to C) at position 17 of exon 3 causing glutamine to histidine change at co don 96 of alpha(2) domain, a conserved position among HLA class I alleles. cDNA sequence analysis further revealed the presence of both normally and a bnormally spliced mRNA species in established cell lines. The abnormal spec ies correspond to partial truncation of exon 3 presumably due to the nucleo tide change in exon 3, which constitutes a new consensus accept or splice s ite within this exon. We postulate that the observed blank is essentially t he consequence of qualitative change in a critical region of this novel ant igen as abnormal mRNA species are relatively less abundant than normal spec ies. Because the residue 96 of the HLA class I heavy chain is directly invo lved in interaction with alpha(2)m, another interesting possibility is that an aminoacid change in this position would perturb such interaction and co nsequently could affect the serological specificity of B*3916, or its expre ssion or both. Human Immunology 61, 467-473 (2000). (C) American Society fo r Histocompatibility and Immunogenetics, 2000. Published by Elsevier Scienc e Inc.