Isolation, expression, and the primary structure of HLA-Cw1 and HLA-Cw2 genes: Evolutionary aspects
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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.
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- Guild, B. C., Erikson, R. L., and Strominger, J. L.: HLA-A2 and HLA-B7 antigens are phosphorylated in vitro by Rous sarcoma virus kinase (pp66v-src) at a tyrosine residue encoded in a highly conserved exon of the intracellular domain. Proc. Natl. Acad. Sci. U.S.A. 80: 2894–2898, 1983PubMedGoogle Scholar
- Klein, J. and Figueroa, F.: The evolution of class I MHC genes. Immunol. Today 7: 41–44, 1986aGoogle Scholar
- Klein, J. and Figueroa, F.: Evolution of the major histocompatibility complex. Crit. Rev. Immunol., in press, 1986bGoogle Scholar
- Lopez de Castro, J. A., Barbosa, J. A., Krangel, M. S., Biro, P. A., and Strominger, J. L.: Structural analysis of functional sites of HLA class I antigens. Immunol. Rev. 85: 147–168, 1985Google Scholar
- Rein, R. S., Seemann, H. A., Stam, N., Neefjes, J. J., and Ploegh, H. L.: Association with beta 2-microglobulin controls expression of transfected human class I genes. J. Immunol., in press, 1987Google Scholar
- Southern, P. J. and Berg, P.: Transformation of mammalian cells to antibiotic resistance with a bacterial gene under control of the SV40 early region promoter. J. Mol. App. Genet. 1: 327–341, 1982Google Scholar
- Srivastava, R., Duceman, B. W., Biro, P. A., Chorney, M. J., Sood, A., Greenspan, D. S., Pan, J., and Weissman, S. M.: New approaches and results in cloning of the human major histocompatibility complex. In B. Pernis and H. J. Vogel (eds.): Cell Biology of the Major Histocompatibility Complex, pp. 27–35, Harcourt Brace Jovanovich, New York, 1985bGoogle Scholar