The molecular basis for reactivity of anti-Cw1 and anti-Cw3 alloantisera with HLA-B46 haplotypes

Abstract

HLA haplotypes containing the HLA‐B46 allele react with both anti‐Cw1 and anti‐Cw3 alloantisera, a pattern of reactivity defined as the Cwl1 antigen and postulated to involve either a distinctive Cw11 allele or a duplicated HLA‐C locus. From serological characterization of CIR cells transfected with B46 cDNA we now demonstrate that the anti‐Cw3 reactivity with these haplotypes is solely due to the B46 molecule and not to an HLA‐C molecule. Furthermore, isolation and characterization of HLA‐C mRNA from cells expressing B46 strongly suggest that anti‐Cw1 reactions are directed against the product of a conventional Cw1 allele. The antigenic cross‐reactivities of B46 with B62 and Cw3 correlate with its chimaeric primary structure, which is identical to that of B62, except in the a, helix where it is identical to both Cw3 and Cw1. The structure, distribution and genetic linkage of B46 indicate it is of recent, Asian origin and is the result of a gene conversion, involving Cw1 as the donor gene and B62 as the recipient. These results demonstrate that the Cw11 antigen neither dorresponds to a novel HLA‐C allele nor a duplicated HLA‐C locus, but to a combination of epitopes contributed by linked Cw1 and B46 alleles. The nucleotide sequence we previously and erroneously attributed to a distinct Cwl1 allele is now demonstrated to encode Cw8. Isolation of the cDNA clone with this sequence from a library made from a cell homozygous for the B46 haplotype was probably an artefact of contamination.