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The alpha chain, not the beta chain of HLA-DR antigens participates in activation of T cells in autologous mixed lymphocyte reaction

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Abstract

Using antisera against the alpha, the beta or the complex of both chains of HLA-DR antigens, we have studied the role of individual chains of HLA-DR antigens in activation of T cells in autologous mixed lymphocyte reaction (AMLR). Alpha chain-specific antibody, not anti-beta chain serum prevented T cells from acquiring responsiveness to interleukin-2 (IL-2), suppressed the production of 1L-2, and inhibited the T cell proliferative response in both primary and secondary AMLR cultures. However, proliferation of already activated IL-2 reactive T cells supported by IL-2 was not affected by any of the four different types of anti-DR sera used. Fifty to sixty percent of T cells activated by AMLR or by PHA possessed DR antigens and functioned well as stimulator cells in secondary AMLR cultures. Moreover, the stimulatory activity of these DR-positive T cells was suppressed by the anti-alpha chain, not by the beta chain-specific antibody. Since continuous proliferation of T cells requires IL-2 and since nonactivated T cells are not sensitive to IL-2 and are unable to absorb this growth factor, we conclude the following: (1) The alpha, not the beta chain of HLA-DR antigens seems to be the structure responsible for enabling resting T cells to respond to IL-2 and induce production of IL-2 in AMLR. (2) Once T cells have acquired responsiveness to IL-2 and the growth factor has been produced, there is no further requirement for HLA-DR antigens, but the availability of IL-2 determines the level and extent of proliferation of IL-2 sensitive T cells.

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References

  • Blobel, G. and Dobberstein, B.: Transfer of proteins across membranes. J. Cell. Biol. 67: 835–840, 1975

    Google Scholar 

  • Bonner, W. J. and Laskey, R. A.: A film detection method or tritium labelled proteins and nucleic acids in polyacrylamide gels. Eur. J. Biochem. 46: 83–89, 1974

    Google Scholar 

  • Charron, D. J. and McDevitt, H. O.: Characterization of HLA-D region antigens by two dimension gel electrophoresis. Molecular genotyping. J. Exp. Med. 152: 375–381, 1980

    Google Scholar 

  • Dock, N. L. and Davey, F. R.: Peripheral blood monocytes in the autologous mixed lymphocyte reaction. Clin. Immunol. Immunopathol. 17: 123–128, 1980

    Google Scholar 

  • Emery, D. L. and Morrison, W. L.: Generation of autologous mixed leukocyte reaction during the course of infection with theileria parva (East Coast Fever) in cattle. Immunology 40: 229–234, 1980

    Google Scholar 

  • Engleman, E. G., Charron, D. J., Benike, C. J., and Stewart, G. J.: Ia antigen on peripheral blood mononuclear cells in man. I. Expression, biosynthesis and function of HLA-DR antigen on non-T cells. J. Exp. Med. 152: 99–113, 1980a

    Google Scholar 

  • Engleman, E. G., Benike, C., Hoppe, R. T., Kaplan, H. A., and Berberich, R.: Autologous mixed lymphocyte reaction in patients with hodgkin's disease: evidence for a T cell defect. J. Clin. Invest. 66: 149–154, 1980b

    Google Scholar 

  • Engleman, E. G., Benike, C. J., and Charron, D. J.: Ia antigen on peripheral blood mononuclear leukocytes in man. II. Functional studies of HLA-DR positive T cells activated in mixed lymphocyte reactions. J. Exp. Med. 152: 114–126, 1980c

    Google Scholar 

  • Fitzharris, P. and Knight, R. A.: Generation of suppressor cells in the autologous mixed lymphocyte reaction. Clin. Exp. Immunol. 46: 185–195, 1981

    Google Scholar 

  • Gottlieb, A. B., Fu, S. M., Yu, D. T. Y., Wang, J. P., Halper, J. P., and Kunkel, H. G.: The nature of the stimulatory cell in human allogeneic and autologous MLC functions: role of isolated IgM bearing B cells. J. Immunol. 123: 1749–1756, 1979

    Google Scholar 

  • Hausmman, P. and Stobo, J.: Specificity and function of a human autologous reactive T cell. J. Exp. Med. 149: 1537–1542, 1979

    Google Scholar 

  • Hayman, M. J. and Crumpton, M. J.: Isolation of glycoproteins from pig lymphocyte plasma membrane using Lens culinaris pbytohemagglutinin. Biochem. Biophys. Res. Commun. 47: 923–930, 1972

    Google Scholar 

  • Hom, J. and Talal, N.: Decreased syngeneic mixed lymphocyte response in genetically susceptible autoimmune mice. Fed. Proc. 39: 1129, 1980

    Google Scholar 

  • Innes, J., Kuntz, M., Kim, Y., and Weksler, M.: Induction of suppressor activity in the autologous mixed lymphocyte reaction and in cultures with concanavalin A. J. Clin. Invest. 64: 1608–1611, 1979

    Google Scholar 

  • Kauffman, J. F., Anderssen, R. L., and Strominger, J. L.: HLA-DR antigens have polymorphic light chains and invariant heavy chains as assessed by lysine-containing tryptic peptide analysis. J. Exp. Med. 152: 375–380, 1980

    Google Scholar 

  • Klareskog, L., Träagårdh, L., Rask, L., and Peterson, P. A.: Isolation and characterization of detergent solubilized human HLA-DR transplantation antigens. Biochemistry 18: 1481–1489, 1979

    Google Scholar 

  • Klareskog, L., Träagårdh, L., Lindblom, J. B., and Peterson, P. A.: Reactivity of a rabbit antiserum against highly purified HLA-DR antigens. Scand. J. Immunol. 7: 199–205, 1978

    Google Scholar 

  • Miyasaka, N., Sauvezie, B., Pierce, D. A., Daniels, T. E., and Talal, N.: Decreased autologous mixed lymphocyte reaction in Sjögren's syndrome. J. Clin Invest. 66: 928–933, 1980

    Google Scholar 

  • Möller, G.: T cell stimulating growth factors. Immunol. Rev. 51. 1980

  • Möller, G. (ed.): Acquisition of the T cell repertoire. Immunol. Rev. 42. 1978

  • Moody, C. E., Casazza, B. A., Christensson, W. N., and Weksler, M. E.: Lymphocyte transformation induced by autologous cells. VIII. Impaired autologous mixed lymphocyte reactivity in patients with acute infectious mononucleosis. J. Exp. Med. 150: 1448–1455, 1979

    Google Scholar 

  • Opelz, G., Takasugi, M., and Terasaki, P. I.: Autologous stimulation of human lymphocyte subpopulations. J. Exp. Med. 142: 1042–1054, 1975

    Google Scholar 

  • Nagy, Z., Baxevanis, C., Ishii, N., and Klein, J.: Ia antigens as restriction molecules in IR gene controlled T-cell proliferation. Immunol. Rev. 60: 59–83, 1981

    Google Scholar 

  • Palacios, R., Llorente, L., Alarcón-Segovia, D., Ruiz-Arguelles, A., and Diaz-Jouanen, E.: Autologous rosette forming T cells as the responding cells in autologous mixed lymphocyte reaction. J. Clin. Invest. 65: 1527–1530, 1980

    Google Scholar 

  • Palacios, R., Alarcón-Segovia, D., Llorente, L., Ruiz-Arguelles, A., and Diaz-Jouanen, E.: Human postthymic precursor cells in health and disease. I. Characterization of the autologous rosette forming T cells as postthymic precursors. Immunology 42: 127–135, 1981a

    Google Scholar 

  • Palacios, R., Möller, G., Claesson, L., and Peterson, P. A.: HLA-DR antigens induce proliferation and cytotoxicity of T cells against haptenated (TNP and FITC) self structures. Immunogenetics 14: 367–382, 1981b

    Google Scholar 

  • Palacios, R. and Alarcón-Segovia, D.: Human postthymic precursor cells in health and disease. III. Role of the autologous rosette forming T cells in generation of spontaneous killer cells in autologous mixed lymphocyte reaction. Scand. J. Immunol. 13: 499–502, 1981a

    Google Scholar 

  • Palacios, R. and Alarcón-Segovia, D.: Human postthymic precursor cells in health and disease. VI. Effect of serum thymic factor on the response of cells from patients with systemic lupus erythematosus or mixed connective tissue disease in autologous mixed lymphocyte reaction. Clin. Immunol. Immunopathol. 18: 362–367, 1981b

    Google Scholar 

  • Palacios, R. and Möller, G.: HLA-DR antigens render resting T cells sensitive to Interleukin-2 and induce production of the growth factor in autologous mixed lymphocyte reaction. Cell. Immunol. 63: 143–153, 1981a

    Google Scholar 

  • Palacios, R. and Möller, G.: Cyclosporin-A blocks receptors for HLA-DR antigens on T cells. Nature 290: 792–794, 1981b

    Google Scholar 

  • Palacios, R.: Role of the autologous rosette forming T cells in Concanavalin-A induced suppressor cell function. Cell. Immunol. 61: 273–279, 1981a

    Google Scholar 

  • Palacios, R.: HLA-DR antigens render Interleukin-2 producer T lymphocytes sensitive to Interleukin-1. Scand. J. Immunol. 14: 321–326, 1981b

    Google Scholar 

  • Palacios, R.: Role of individual chains of HLA-DR antigens in activation of T cells induced by alloantigens. Immunogenetics 14: 309–322, 1981c

    Google Scholar 

  • Ponzio, NM.: Lymphocyte responses to syngeneic antigens. I. Enhancement of the murine autologous mixed lymphocyte reaction by polyethylene glycol. Cell. Immunol. 49: 266–272, 1980

    Google Scholar 

  • Russo, C., Indiveri, F., Quaranta, V., Molinaro, G. A., Pellegrino, M. A., and Ferrone, S.: Stimulation of human T lymphocytes by PHA-activated autologous T lymphocytes: Analysis of the role of Ia-like antigens with monoclonal antibodies. Immunogenetics 12: 267–274, 1981

    Google Scholar 

  • Sakane, T., Steinberg, A., and Green, I. Failure of autologous mixed lymphocyte reactions between T and non-T cells in patients with systemic lupus erythematosus. Proc. Natl. Acad. Sci. U.S.A. 75: 3464–3469, 1978

    Google Scholar 

  • Sakane, T. and Green, L: Specificity and suppressor function of human T cells responsive to autologous non-T cells. J. Immunol. 123: 584–589, 1979

    Google Scholar 

  • Smith, K. A., Lachman, L. B., Oppenheim, J. J., and Favata, M. F.: The functional relationship of Interleukins. J. Exp. Med. 151: 1551–1556, 1980

    Google Scholar 

  • Sugawara, I. and Palacios, R.: Interleukin-2 and serum thymic factor allow the autologous rosette forming T cells to develop helper and cytotoxic functions. Scand. J. Immunol., in press, 1982

  • Thorsby, E. and Nousiainen, H.: In vitro sensitization of human T lymphocytes to hapten (TNP)conjugated and non-treated autologous cells is restricted by self HLA-D. Scand. J. Immunol. 9: 183–192, 1979

    Google Scholar 

  • Tomanari, K.: Cytotoxic T Cells generated in the autologous mixed lymphocyte reaction. I. Primary autologous mixed lymphocyte reaction. J. Immunol. 124: 1111–1121, 1980

    Google Scholar 

  • Tomonari, K., Wakisaka, A., and Aizawa, M.: Self recognition by autologous mixed lymphocyte reaction-primed cells. J. Immunol. 125: 1596–164, 1980

    Google Scholar 

  • Tötterman, T. H., Nilsson, K., and Sundström, C.: Phorbol ester-induced differentiation of chronic lymphocytic leukemia cells. Nature 288: 176–178, 1980

    Google Scholar 

  • Yamashita, U. and Shevach, E. M.: The syngeneic mixed lymphocyte reaction: the genetic requirements for the recognition of self resemble the requirements for the recognition of antigen in asssociation with self. J. Immunol. 124: 1773–1780, 1980

    Google Scholar 

  • Yu, D. T. Y., Molune, J. M., Fu, S. M., Winchester, R. J., and Kunkel, H. G.: Two types of la-positive T cells. Synthesis and exchange of Ia antigens. J. Exp. Med. 152: 89–96, 1980

    Google Scholar 

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Authors and Affiliations

  1. Department of Immunobiology, Wallenberg Laboratory, Karolinska Institute, Lilla Frescati, S-104 05, Stockholm, Sweden

    Ronald Palacios, Göran Möller & Erna Möller

  2. Department of Cell Research, Wallenberg Laboratory, University of Uppsala, Uppsala, Sweden

    Lena Claesson & Per A. Peterson

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  1. Ronald Palacios
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  2. Lena Claesson
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  3. Göran Möller
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  4. Per A. Peterson
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  5. Erna Möller
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Palacios, R., Claesson, L., Möller, G. et al. The alpha chain, not the beta chain of HLA-DR antigens participates in activation of T cells in autologous mixed lymphocyte reaction. Immunogenetics 15, 341–356 (1982). https://doi.org/10.1007/BF00364258

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  • DOI: https://doi.org/10.1007/BF00364258

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