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

Tissue Antigens. 1992 May;39(5):249-57. doi: 10.1111/j.1399-0039.1992.tb01943.x.

Abstract

HLA haplotypes containing the HLA-B46 allele react with both anti-Cw1 and anti-Cw3 alloantisera, a pattern of reactivity defined as the Cw11 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 alpha 1 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 corresponds 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 Cw11 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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alleles
  • Amino Acid Sequence
  • Antigen-Antibody Reactions / genetics*
  • Artifacts*
  • Base Sequence
  • Consensus Sequence
  • Cross Reactions
  • DNA / isolation & purification*
  • Epitopes / genetics
  • Epitopes / immunology
  • Genes, MHC Class II*
  • HLA-C Antigens / genetics*
  • HLA-C Antigens / immunology*
  • Haplotypes
  • Humans
  • Isoantibodies / immunology*
  • Models, Molecular
  • Molecular Sequence Data
  • Polymorphism, Genetic
  • Protein Conformation
  • Recombinant Proteins / immunology
  • Sequence Alignment
  • Terminology as Topic

Substances

  • Epitopes
  • HLA-C Antigens
  • HLA-C*03 antigen
  • HLA-C*08 antigen
  • HLA-Cw1 antigen
  • HLA-Cw11 antigen
  • Isoantibodies
  • Recombinant Proteins
  • DNA

Associated data

  • GENBANK/M84171
  • GENBANK/M84172
  • GENBANK/M84173
  • GENBANK/M84174