, Volume 25, Issue 5, pp 313-322

First online:

Isolation, expression, and the primary structure of HLA-Cw1 and HLA-Cw2 genes: Evolutionary aspects

  • Detlef GüssowAffiliated withThe Netherlands Cancer Institute
  • , Rita S. ReinAffiliated withThe Netherlands Cancer Institute
  • , Ingeborg MeijerAffiliated withThe Netherlands Cancer Institute
  • , Wout de HoogAffiliated withThe Netherlands Cancer Institute
  • , Gerhard H. A. SeemannAffiliated withThe Netherlands Cancer Institute
  • , Frans M. HochstenbachAffiliated withThe Netherlands Cancer Institute
  • , Hidde L. PloeghAffiliated withThe Netherlands Cancer Institute

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The HLA-Cw1 and -Cw2 genes were identified in a genomic library and their products characterized by biochemical methods. The HLA-Cw and -Cw2 genes, upon transfection in mouse L cells, give rise to class I antigen heavy chains that associate with neither mouse nor human beta-2 microglobulin. They are indistinguishable in isoelectric point from polypeptides identified as HLA-Cw1 and -Cw2 in human cells. The nucleotide sequence of HLA-Cw1 and -Cw2 and their comparison with HLA-Cw3, the only other known HLA-C sequence, reveal a characteristic pattern of locus-specific amino acids. A comparison of 13 different human class I primary structures leads us to speculate that the most variable region in HLA class I antigens, positions 61–83, could assume an alpha helical structure of critical importance for class I antigen function. The locus specificity and the higher degree of intralocus conservation in the COON-terminal region, especially in the transmembrane and cytoplasmic domains, must reflect evolutionary ancestry rather than positive selection. In view of the pattern and types of substitutions observed for HLA-C locus products, their function as immune response gene products is questioned.