Abstract
The serological reactivities of HLA-A3, -B7, and -CW3 heavy chains associated with either mouse, bovine, or human beta-2 microglobulin (β 2m) and expressed on the surface of transfected mouse fibroblasts were analyzed. All reactivities associated with one cluster (defined by monoclonal antibody W6/32) of antigenic determinants expressed by these HLA class I molecules were lost, or profoundly reduced, after each heavy chain associated with mouse β 2-m. Expression by the transfected fibroblasts of the HLA-A3, -B7, and -CW3 heavy chains in association with human β 2m restores these reactivities. Since most of the amino acid differences between mouse and human β 2m probably correspond to externally oriented hydrophilic residues, these results suggest that critical interactions in the three-dimensional structure of HLA class I molecules occur between the light chain and the first two external domains of the class I heavy chains, to which some of the altered reactivities have been mapped.
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Arce-Gomez, B., Jones, A. E., Barnstable, C. J., Solomon, E., and Bodmer, W. F.: The genetic control of HLA-A and B antigens in somatic cell hybrids: Requirement for β2-microglobulin. Tissue Antigens 11: 96–112, 1978
Barbosa, J. A., Karmack, M. E., Biro, P. A., Weissman, S. M., and Ruddle, F. H.: Identification of human genomic clones coding the major histocompatibility antigens HLA-A2 and HLA-B7 by DNA-mediated gene transfer. Proc. Natl. Acad. Sci. U.S.A. 79: 6327–6331, 1982
Becker, J. W., Ziffer, J. A., Edelman, G. M., and Cunningham, B. A.: Crystallographic studies of bovine β2-microglobulin. Proc. Natl. Acad. Sci. U.S.A. 74: 3345–3349, 1977
Berger, A. E., Davis, J. E., and Cresswell, P.: Monoclonal antibody to HLA-A3. Hybridoma 1: 87–90, 1982
Bernabeu, C., Finley, D., van de Rijn, M., Maziarz, R. T., Biro, P. A., Spits, H., De Vries, J., and Terhorst, C. M.: Expression of the major histocompatibility antigens HLA-A2 and HLA-B7 by DNA mediated gene transfer. J. Immunol. 131: 2032–2037, 1983
Bernabeu, C., van de Rijn, N., Lerch, N. G., and Terhorst, P.: β2-microglobulin from serum associates with MHC class I antigens on the surface of cultured cells. Nature 308: 642–645, 1984
Brodsky, F. M. and Parham, P.: Monomorphic anti-HLA-A, B, C monoclonal antibodies detecting molecular subunits and combinatorial determinants. J. Immunol. 128: 129–135, 1982
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
Buccini, D., Lasserre, C., Kunst, F., Lovell-Badge, R., Pictet, R., and Jami, J.: Stable transformation of mouse teratocarcinoma stem cells with the dominant selective marker Eco. Gpt and retention of their development potentialities. EMBO J. 2: 229–232, 1983
Colbere-Garapin, F., Horodniceanu, F., Kourilsky, P., and Garapin, A. C.: A new dominant hybrid selective marker for higher eukaryotic cells. J. Mol. Biol. 150: 1–14, 1981
Deisenhofer, J.: Crystallographic refinement and atonic models of a human Fc fragment and its complex with fragment B of protein A from Staphylococcus aureus at 2.9 and 2.8 Å resolution. Biochemistry 20: 2361–2370, 1981
Delaizes, P. and Wodak, S.: Prograph: An interactive graphic system dedicated to the visualisation and manipulation of biological macromolecules. In M. Balaban, J. L. Sussman, W. Traub, and A. Youath (eds.): Structural Aspect of Recognition and Assembly in Biological Macromolecules, Volume 1, pp. 169–181, Ballaban ISS, Rehovot, Philadelphia, 1981
Edelman, G. M., Cunningham, B. A., Gall, W. E., Gottlieb, P. D., Rutishauser, U., and Waxdal, M. J.: The covalent structure of an entire γG immunoglobulin molecule. Proc. Natl. Acad. Sci. U.S.A. 63: 78–85, 1969
Ellis, S. A., Taylor, C., and McMichael, A.: Recognition of HLA-B27 and related antigen by a monoclonal antibody. Hum. Immunol. 5: 49–59, 1982
Engelhard, V. H. and Benjamin, C.: Xenogeneic cytotoxic T-cell clones recognize alloantigenic determinants on HLA-A2. Immunogenetics 18: 461–473, 1983
Fellous, M., Kamoun, M., Wiels, J., Dausset, J., Clements, G., Zeuthen, J., and Klein, G.: Induction of HLA expression in Daudi cells after cell fusion. Immunogenetics 5: 423–436, 1977
Groves, M. L. and Greenberg, R.: Complete amino acid sequence of bovine β2-microglobulin. J. Biol. Chem. 257: 2619–2626, 1982
Herman, A., Parham, P., Weissman, S. M., and Engelhard, P.: Recognition by xenogeneic cytotoxic T lymphocytes of cells expressing HLA-A2 or HLA-B7 after DNA-mediated gene transfer. Proc. Natl. Acad. Sci. U.S.A. 80: 5056–5060, 1983
Hyafil, F. and Strominger, J. L.: Dissociation and exchange of the β2-microglobulin subunit of HLA-A and HLA-B antigens. Proc. Natl. Acad. Sci. U.S.A. 76: 5834–5838, 1979
Jordan, B. R., Lemonnier, F. A., Caillol, D. H., and Trucy, J.: Transformation of murine LMTK− cells with purified HLA class I genes. III. Human HLA class I antigens coded by hybrid genes constructed in vitro indicate association of serologic reactivities with the first two domains of the molecule. Immunogenetics 18: 165–171, 1983
Kavathas, P. and Herzenberg, L. A.: Stable transformation of mouse L cells for human membrane T cells differentiation antigens, HLA and β2-microglobulin: Selection by fluorescein activated cell sorting. Proc. Natl. Acad. Sci. U.S.A. 80: 524–528, 1983
Kefford, R. K., Calabi, F., Fearnley, I. M., Burrone, O. R., and Milstein, C.: Serum β2-microglobulin binds to a T-cell differentiation antigen and increases its expression. Nature 308: 641–642, 1984
Lancet, D., Parham, P., and Strominger, J. L.: Heavy chain of HLA-A and HLA-B antigens is conformationally labile: A possible role for β2-microglobulin. Proc. Natl. Acad. Sci. U.S.A. 76: 3844–3848, 1979
Lemonnier, F. A., Malissen, M., Golstein, P., Le Bouteiller, P., Rebai, N., Damotte, M., Birnbaum, D., Caillol, D., Tracy, J., and Jordan, B. R.: Expression of human class I histocompatibility antigens at the surface of DNA-transformed mouse L-cells. Immunogenetics 16: 355–361, 1982
Lemonnier, F. A., Le Bouteiller, P. P., Olive, D., Malissen, B., Mishal, Z., Layet, C., Dubreuil, J., Caillol, D. H., Kourilsky, F. M., and Jordan, B. R.: Transformation of LMTK− cells with purified HLA class I genes. V. Antibody-induced structural modification of HLA class I molecules results in potentiation of the fixation of a second monoclonal antibody. J. Immunol. 132: 1176–1182, 1984
Liabeuf, A., Le Borgne de Kaoel, C., Kourilsky, F. M., Malissen, B., Manuel, Y., and Sanderson, A. R.: An antigenic determinant of human β2-microglobulin masked by the association with HLA heavy chains at the cell surface: Analysis using monoclonal antibodies. J. Immunol. 127: 1542–1548, 1981
Rebai, N., Mercier, P., Kristensen, T., Devaux, C., Malissen, B., Mawas, C., and Pierres, M.: Murine H-2Dd-reactive monoclonal antibodies recognize shared antigenic determinant(s) on human HLA-B7 or HLA-B27 molecules or both. Immunogenetics 17: 357–370, 1983
Schmidt, W., Fèstenstein, H., Ward, P. J., and Sanderson, A. R.: Interspecies exchange of β 2-microglobulin and associated MHC and differentiation antigens. Immunogenetics 13: 483–491, 1981
Vega, M. A., Bragado, R., Ezquerra, A., and Lopez de Castro, J. A.: Variability and conformation of HLA class I antigen: A predictive approach to the spatial arrangement of polymorphic regions. Biochemistry 23: 823–831, 1984
Yokoyama, K. and Nathenson, S. G.: Intramolecular organisation of class I H-2 MHC antigens: Localization of the alloantigenic determinants and the β2-m binding site to different regions of the H-2K b glycoprotein. J. Immunol. 130: 1419–1425, 1983
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Ferrie, P., Fontecilla-Camps, J.C., Bucchini, D. et al. Altered structure of HLA class I heavy chains associated with mouse beta-2 microglobulin. Immunogenetics 21, 321–331 (1985). https://doi.org/10.1007/BF00430798
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DOI: https://doi.org/10.1007/BF00430798