Abstract
Two new HLA-C alleles, Cw*0333 and Cw*0217, were identified in a Black South African population. HLA-Cw*0333 differs from Cw*030201 by an A-->G substitution at nucleotide 323, yielding an unusual missense substitution of Cys for the conserved Tyr-84 at the antigen cleft terminus. Molecular modeling suggests that this alters the predicted interactions of this critical residue with the opposite alpha(2)-helix, the peptide COOH terminus and possibly KIR2DL2. The second allele, Cw*0217, differs from Cw*0205 by an A-->T substitution at nucleotide 368, resulting in a Tyr-->Phe substitution at residue 99 of the HLA-C beta-pleated sheet that likely influences peptide side-chain binding. Both Cw*0333 and Cw*0217 appear to have arisen by missense mutations, respectively, from the HLA-B*5801-Cw*0302 and B*080101-Cw*0205 haplotypes.