The molecular basis for reactivity of anti-Cw1 and anti-Cw3 alloantisera with HLA-B46 haplotypes.
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.
Zemmour
J
J
Department of Cell Biology, Stanford University, CA.
Gumperz
J E
JE
Hildebrand
W H
WH
Ward
F E
FE
Marsh
S G
SG
Williams
R C
RC
Parham
P
P
D000483:Alleles; D000595:Amino Acid Sequence; D000937:Antigen-Antibody Reactions / Q000235:genetics*; D016477:Artifacts; D001483:Base Sequence; D016384:Consensus Sequence; D003429:Cross Reactions; D004247:DNA / Q000302:isolation & purification*; D000939:Epitopes / Q000235:genetics / Q000276:immunology; D005802:Genes, MHC Class II; D015236:HLA-C Antigens / Q000235:genetics* / Q000276:immunology*; D006239:Haplotypes; D006801:Humans; D007518:Isoantibodies / Q000276:immunology*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000276:immunology; D016415:Sequence Alignment; D009626:Terminology as Topic
D000939:Epitopes; D015236:HLA-C Antigens; C038653:HLA-C*03 antigen; C524551:HLA-C*08 antigen; C047431:HLA-Cw1 antigen; C069021:HLA-Cw11 antigen; D007518:Isoantibodies; D011994:Recombinant Proteins; D004247:DNA