Intracellular transport of class I MHC molecules in antigen processing mutant cell lines.
Intracellular transport and stability of class I MHC glycoproteins depends on the assembly of H chain, beta 2-microglobulin, and peptide. The Ag processing mutant cell lines T2 and RMA-S have defects in peptide loading of class I, resulting in reduced cell surface expression of class I molecules. Expression of class I molecules in the murine cell line RMA-S can be induced at 26 degrees C, suggesting that they are transported to the cell surface, but are unstable. However, most human class I molecules in T2 are poorly expressed at the cell surface, even at 26 degrees C. To directly compare the transport of human and mouse alleles in RMA-S and T2, the human alleles HLA-A2, A3, and B27 were transfected into RMA-S along with human beta 2-microglobulin, and the mouse alleles H-2Kb and Db were transfected into T2. Surface expression of HLA-A3 and B27 in RMA-S remained less than 10% of wild-type levels at 26 degrees C. H-2Kb and Db in both cell lines, however, were expressed at 20 to 30% wild-type levels at 37 degrees C and could be induced to wild-type levels at 26 degrees C or with peptides. The selective expression of murine class I glycoproteins at the cell surface of T2 is not because of their greater stability when associated with human beta 2m, since H-2Kb and Db H chain/human beta 2m complexes dissociate more rapidly in vitro than HLA-A3 and B27 complexes. These results suggest that the difference in transport between human and mouse class I in T2 reflects a fundamental structural property of the class I glycoproteins.
Section of Immunobiology, Howard Hughes Medical Institute, Yale University Medical School, New Haven, CT 06510.
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KS
Anderson
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Alexander
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M
Wei
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Cresswell
D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D000938:Antigen-Presenting Cells / Q000378:metabolism*; D001692:Biological Transport; D005805:Genes, MHC Class I; D015395:Histocompatibility Antigens Class I / Q000032:analysis / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014407:Tumor Cells, Cultured; D001613:beta 2-Microglobulin / Q000378:metabolism
D015395:Histocompatibility Antigens Class I; D001613:beta 2-Microglobulin