Isolation, expression, and the primary structure of HLA-Cw1 and HLA-Cw2 genes: evolutionary aspects.
The HLA-Cw1 and -Cw2 genes were identified in a genomic library and their products characterized by biochemical methods. The HLA-Cw1 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 COOH-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.
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D001483:Base Sequence; D005075:Biological Evolution; D002460:Cell Line; D004247:DNA / Q000302:isolation & purification; D004262:DNA Restriction Enzymes; D005796:Genes; D006680:HLA Antigens / Q000235:genetics*; D015236:HLA-C Antigens; D006801:Humans; D007739:L Cells / Q000276:immunology; D051379:Mice; D009710:Nucleotide Mapping
D006680:HLA Antigens; D015236:HLA-C Antigens; C048767:HLA-C*02 antigen; C047431:HLA-Cw1 antigen; D004247:DNA; D004262:DNA Restriction Enzymes