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Differential transport requirements of HLA and H-2 class I glycoproteins

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Abstract

Transport of human and mouse major histocompatibility complex class I glycoproteins has been examined in a transport deficient B-lymphoblastoid cell line × T-lymphoblastoid cell line (B-LCL × T-LCL) hybrid, 174 × CEM. T2 (T2). This cell line expresses no detectable endogenous HLA-B5 and reduced levels of HLA-A2 on its surface although these molecules are synthesized. In order to study this defect further, either HLA-Bw58 or HLA-B7 genomic clones were transfected into T2. Metabolic labeling and immune precipitation demonstrated biosynthesis of the Bw58 or 137 glycoprotein. However, like the endogenous HLA-B5 molecule, neither HLA-Bw58 nor HLA-B7 was expressed at the cell surface. The cloned genes were properly expressed on the surface of C1R, a control B-LCL. To determine if mouse class I alleles had the same transport requirements as the human class I glycoproteins, either mouse H-2D por H-2K b class I genes were introduced into T2. Surprisingly, the H-2 class I glycoproteins were transported to the cell surface normally. These data suggest a fundamental difference between human and mouse histocompatibility antigens in their requirements for intracellular transport.

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References

  • Allen, H. Fraser, J., Flyer, D., Calvin, S., and Flavell, R.: β 2-Microglobulin is not required for cell surface expression of the murine class I histocompatibility antigen H-2Db or of a truncated H-2Db. Proc Nod Acad Sci USA 83: 7447–7451, 1986

    Google Scholar 

  • Barbosa, J. A., Santos-Aquado, J., Mentzer, S. J., Strominger, J. L., Burakoff, S. J., and Biro, P. A.: Site-directed mutagenesis of class I HLA genes. J Exp Med 166: 1329–1350, 1987

    Google Scholar 

  • Berger, A. E., Davis, J. E., and Cresswell, P.: Monoclonal antibody to HLA-A3. Hybridoma 1: 87–90, 1982

    Google Scholar 

  • Brodsky, F. M., Parham, P., Barnstable, C. J., Crumpton, M. J., and Bodmer, W. F.: Monoclonal antibodies for analysis of the HLA system. Immunol Rev 47: 3–61, 1979

    Google Scholar 

  • Coligan, J. E., Kindt, T. J., Vehara, H., Martinko, J., and Nathenson, S. G.: Primary structure of a murine transplantation antigen. Nature 291: 35–39, 1981

    Google Scholar 

  • Cresswell, P. and Ayres, J. L.: HLA antigens: rabbit antisera reacting with all A series or all B series specificities. Eur J Immunol 6: 794–799, 1976

    Google Scholar 

  • Cresswell, P., Springer, T. A., Strominger, J. L., Turner, M. J., Grey, H. M., and Kubo, R. I.: Immunological identity ofthe small subunit of HLA antigens and B2-microglobulin and its turnover in the cell membrane. Proc Natl Acad Sci USA 71: 2123–2127, 1974

    Google Scholar 

  • Darsley, M. J., Takahashi, H., Macchi, M. J., Frelinger, J. A., Ozato, K., and Appella, E.: New family of exon-shuffled recombinant genes reveals extensive interdomain interactions in class I histocompatibility antigens and identifies residues involved. J Exp Med 165: 211–222, 1987

    Google Scholar 

  • DeMars, R.: Mutations that dissect the D-region of a human B-lymphoblastoid cell line. Dis Markers 2: 175–182, 1984a

    Google Scholar 

  • DeMars, R., Chang, C. C., Shaw, S., Reitnauer, P. J., and Sondel, P. M.: Homozygous deletions that simultaneously eliminate expressions of class I and class II antigens of EBV-transformed B-lymphoblastoid cells. I. Reduced proliferative responses of autologous and allogeneic T cells to mutant cells that have decreased expression of class II antigens. Hum Immunol 11: 77–97, 1984b

    Google Scholar 

  • DeMars, R., Rudersdorf, R., Chang, C., Petersen, J., Strandtmann, J., Korn, N., Sidwell, B., and Orr, H.: Mutations that impair a posttranscriptional step in expression of HLA-A and -B antigens. Proc Natl Acad Sci USA 82: 8183–8187, 1985

    Google Scholar 

  • Edwards, P. A., Smith, C. M., Neville, A. M., and O'Hare, M. J.: A human-human hybridoma system based on a fast-growing mutant of the ARH-77 plasma cell leukemia-derived line. Ear J Immunol 12: 641–648, 1982

    Google Scholar 

  • Engelhard, V. H., Yannelli, J. R., Evans, G. A., Walk, S. F., and Holterman, M. J.: Construction of novel class I histocompatibility antigens by interspecies exon shuffling. J Immunol 134: 4218–4225, 1985

    Google Scholar 

  • Ennis, P. D., Jackson, A. P., and Parham, P.: Molecular cloning of bovine class I MHC cDNA. J Immunol 141: 642–651, 1988

    Google Scholar 

  • Evans, G. A., Margulies, D. M., Camerini-Otero, R. D., Ozato, K., and Seidman, J. G.: Structure and expression of a mouse major histocompatibility antigen gene, H-2Ld. Proc Natl Acad Sci USA 79: 1994–1998, 1982

    Google Scholar 

  • Foley, G. E., Lazarus, H., Farber, S., Uzman, B. G., Boone, B. A., and McCarthy, R. E.: Continuous culture of human lymphoblasts from peripheral blood of a child with acute leukemia. Cancer 18: 522–529, 1965

    Google Scholar 

  • Fraser, J. D., Allen, H., Flavell, R. A., and Strominger, J. L.: Cellsurface expression of H-2Db requires N-linked glycans. Immunogenetics 26: 31–35, 1987

    Google Scholar 

  • Goodfellow, P. N., Jones, E. A., van Heyningen, V., Soloman, E., Bobrow, M., Miggiano, V., and Bodmer, W. F.: The β 2-microglobulin gene is on chromosome 15 and not in the HLA-A region. Nature 254: 267–269, 1975

    Google Scholar 

  • Hansen, T. H., Myers, N. B., and Lee, D. R.: Studies of two antigenic forms of Ld with disparate β 2- microglobulin (β 2m) associations suggest that β 2m facilitates the folding of the α1 and α2 domains during de novo synthesis. J Immunol 140: 3522–3527, 1988

    Google Scholar 

  • Harmon, R. C., Stein, N., and Frelinger, J. A.: Monoclonal antibodies reactive with H-2 determinants. Immunogenetics 18: 541–545, 1983

    Google Scholar 

  • Herrera, V. L. M., Emmanuel, J. R., Ruiz-Opago, N., Levenson, R., and Nodal-Ginart, B.: Three differentially expressed Na, K-ATPase subunit isoforms: structure and functional implications. J Cell Biol 105: 1855–1865, 1987

    Google Scholar 

  • Howell, D. M., Kostyu, D. D., Ting, J. P.-Y., and Cresswell, P.: Expression of class I histocompatibility antigens on human T-B lymphoblast hybrids. Somatic Cell Mol Genet 10: 217–224, 1984

    Google Scholar 

  • Klein, J.: Biology of the Mouse Histocompatibility Complex, Springer, Berlin, 1975

    Google Scholar 

  • Klein, J. and Figueroa, F.: The evolution of class I MHC genes. Immunol Today 7: 41–44, 1986

    Google Scholar 

  • Krangel, M. S., Orr, H. T., and Strominger, J. L.: Assembly and maturation of HLA-A and HLA-B antigens in vivo. Cell 18: 979–991, 1979

    Google Scholar 

  • Landolfi, N. F., Rich, R. R., and Cook, R. G.: Differential glycosylation requirements for the cell-surface expression of class I molecules. J Immunol 134: 423–430, 1985

    Google Scholar 

  • Machamer, C. E. and Cresswell, P.: Biosynthesis and glycosylation of the invariant chain associated with HLA-DR antigens. J Immunol 129: 2564–2569, 1982

    Google Scholar 

  • Maloy, W. L. and Coligan, J. E.: Primary structure of the H-2Db alloantigen. II. Additional amino acid sequence information, localization of a third site of glycosylation and evidence for K and D region specific sequences. Immunogenetics 16: 11–22, 1982

    Google Scholar 

  • Martinko, J. M., Anderson, S. J., and Potter, T.: A murine cell line defective in expression of several class I molecules. Immunogenetics 23: 64–66, 1986

    Google Scholar 

  • McMichael, A. J., Parham, P., Rust, N., and Brodsky, F.: A monoclonal antibody that recognizes an antigenic determinant shared by HLA-A2 and B17. Hum Immunol 1: 121–129, 1980

    Google Scholar 

  • Miyazaki, J.-I., Apella, E., Zhao, H., Forman, J., and Ozato, K.: Expression and function of a nonglycosylated major histocompatibility class I antigen. J Exp Med 163: 856–871, 1986

    Google Scholar 

  • Murray, R., Hutchinson, C. A., III, and Frelinger, J. A.: Saturation mutagenesis of a major histocompatibility complex protein domain: identification of a single conserved amino acid important for allorecognition. Proc Natl Acad Sci USA 85: 3535–3539, 1988

    Google Scholar 

  • O'Farrell, P. Z., Goodman, H. M., and O'Farrell, P. H.: High resolution two-dimensional electrophoresis of basic as well as acidic proteins. Cell 12: 1133–1142, 1977

    Google Scholar 

  • Owen, M. H., Kissonerghis, A.-M., and Lodish, H. F.: Biosynthesis of HLA-A and HLA-B antigens in vivo. J Biol Chem 255: 9678–9684, 1980

    Google Scholar 

  • Parham, P., Alpert, B. N., Orr, H. T., and Strominger, J. L.: Carbohydrate moiety of HLA antigens: antigenic properties and amino acid sequences around the site of glycosylation. J Biol Chem 252: 7555–7567, 1977

    Google Scholar 

  • Ploegh, H. L., Orr, H. T., and Strominger, J. L.: Major histocompatibility antigens: the human (HLA-A, -B, -C) and routine (H-2K, H-2D) class I molecules. Cell 24: 287–299, 1981a

    Google Scholar 

  • Ploegh, H. L., Orr, H. T., and Strominger, J. L.: Biosynthesis and cell surface localization of the nonglycosylated human histocompatibility antigens. J Immunol 126: 270–275, 1981b

    Google Scholar 

  • Potter, T. A., Boyer, C., Schmitt-Verhulst, A.-M., Goldstein, P., and Rajan, T. V.: Expression of H-2Db on the cell surface in the absence of detectable β 2 microglobulin. J Exp Med 160: 317–322, 1984

    Google Scholar 

  • Salter, R. D. and Cresswell, P.: Impaired assembly and transport of HLA-A and -B antigens in a mutant T × B cell hybrid. EMBO J 5: 943–949, 1986

    Google Scholar 

  • Salter, R. D., Howell, D. N., and Cresswell, P.: Genes regulating HLA class I antigen expression in T-B lymphoblast hybrids. Immunogenetics 21: 235–246, 1985a

    Google Scholar 

  • Salter, R. D., Alexander, J., Levine, F., Pious, D., and Cresswell, P.: Evidence for two trans-acting genes regulating HLA class II antigen expression. J Immunol 135: 4235–4238, 1985b

    Google Scholar 

  • Sege, K., Rask, L., and Peterson, P. A.: Role of β 2m in the intracellular processing of HLA antigens. Biochemistry 20: 4523–4530, 1981

    Google Scholar 

  • Severinsson, L. and Peterson, P. A.: β 2m induces intracellular transport of human class I transplantation antigen heavy chains in Xenopus laevis oocytes. J Cell Biol 99: 226–232, 1984

    Google Scholar 

  • Shimizu, Y., Koller, B., Geraghty, D., Orr, H., Shaw, S., Kavathas, P., and DeMars, R.: Transfer of cloned human class I major histocompatibility complex genes into HLA mutant human lymphoblastoid cells. Mol Cell Biol 6: 1074–1087, 1986

    Google Scholar 

  • Ways, J. P., Coppin, H. L., and Parham, P.: The complete primary structure of HLA-Bw58. J Biol Chem 260: 11924–11933, 1985

    Google Scholar 

  • Yang, S. Y., Morishima, Y., Collins, N. H., Alton, T., Pollack, M. S., Yunis, E. J., and Dupont, B.: Comparison of one-dimensional IEF patterns for serologically detectable HLA-A and -B allotypes. Immunogenetics 19: 217–231, 1984

    Google Scholar 

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Alexander, J., Payne, J.A., Murray, R. et al. Differential transport requirements of HLA and H-2 class I glycoproteins. Immunogenetics 29, 380–388 (1989). https://doi.org/10.1007/BF00375866

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  • DOI: https://doi.org/10.1007/BF00375866

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