Abstract
The present studies indicate that one can dissect both the heterogeneity and functional program of the human T-cell. These investigations indicate that late in thymic ontogeny the T-cell receptor, which is involved in both antigen recognition and T-cell activation, develops. The receptor is a 90,000 mol. wt heterodimer containing constant and variable regions in its individual alpha and beta chains, which are structurally related to the immunoglobulin molecule. This structure in association with the 20/25,000 mol. wt monomorphic T3 molecule makes up the T-cell receptor complex. It is believed that these unique cell surface glycoproteins will have a critical role in controlling the immune response in man.
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References
Reinherz E L, Schlossman S F: The differentiation and function of human T-lymphocytes.Cell 19, 821 (1980).
Reinherz E L, Schlossman S F: Current concepts in immunology: regulation of the immune response— Inducer and suppressor T-lymphocyte subsets in human beings.New Engl J Med 303, 370 (1980).
Reinherz E L, Meuer S C, Schlossman S F: The human T cell receptor analysis with cytotoxic T cell clones.Immunol Rev 74, 83 (1983).
Reinherz E L, Kung P C, Goldstein G, Levey R H, Schlossman S F: Discrete stages of human intrathymic differentiation: analysis of normal thymocytes and leukemic lymphoblasts of T-cell lineage.Proc Natn Acad Sci USA 77, 1588 (1980).
Meuer S C, Fitzgerald K A, Hussey R E, Hodgdon J C, Schlossman S F, Reinherz E L: Clonotypic structures involved in antigen-specific human T cell function. Relationship to the T3 molecular complex.J Exp Med 157, 705 (1983).
Umiel T, Daley J F, Bhan A K, Levey R H, Schlossman S F, Reinherz E L: Acquisition of immune competence by a subset of human cortical thymocytes expressing mature T cell antigens.J Immun 129, 1054 (1982).
Acuto O, Hussey R E, Fitzgerald K A, Proteintis J P, Meuer S C, Schlossman S F, Reinherz E L: The human T cell receptor: appearance in ontogeny and biochemical relationship of alpha and beta subunits on IL-2 dependent clones and T cell tumors.Cell 34, 717 (1983).
Reinherz E L, Schlossman S F: In Fefer A (ed),The Potential Role of T Subpopulation in Cancer Therapy, p. 253. New York, Raven Press (1982).
Meuer S C, Hussey R E, Fabbi M, Fox D, Acuto O, Fitzgerald K A, Hodgdon J C, Protentis J P, Schlossman S F, Reinherz E L: An alternative pathway of T-cell activation: a functional role for the 50 kd T11 sheep erythrocyte receptor protein.Cell 36, 897 (1984).
Evans R L, Lazarus H, Penta A C, Schlossman S F: Two functionally distinct subpopulations of human T cells that collaborate in the generation of cytotoxic cells responsible for cell-mediated lympholysis.J Immun 120, 1423 (1978).
Reinherz E L, Schlossman S F: Con A-inducible suppression of MLC: evidence for mediation by the TH2+T cell subset in man.J Immun 122, 1335 (1979).
Reinherz E L, Kung P C, Goldstein G, Schlossman S F: Separation of functional subsets of human T cells by a monoclonal antibody.Proc Natn Acad Sci USA 76, 4061 (1979).
Reinherz E L, Kung P C, Goldstein G, Schlossman S F: A monoclonal antibody reactive with the human cytotoxic/suppressor T cell subset previously defined by a heteroantiserum termed TH2.J Immun 124, 1301 (1980).
Meuer S C, Schlossman S F, Reinherz E L: Clonal analysis of human cytotoxic T lymphocytes: T4+ and T8+ effector T cells recognize products of different major histocompatibility complex regions.Proc Natn Acad Sci USA 79, 4395 (1982).
Bensussan A, Meuer S C, Schlossman S F, Reinherz E L: Delineation of an immunoregulatory amplifier population recognizing autologous Ia molecules. Analysis with human T cell clones.J Exp Med 159, 559 (1984).
Meuer S C, Acuto O, Hussey R E, Hodgdon J C, Fitzgerald K A, Schlossman S F, Reinherz E L: Evidence for the T3 associated 90K heterodimer as the T cell antigen receptor.Nature 303, 808 (1983).
Reinherz E L, Hussey R E, Schlossman S F: A monoclonal antibody blocking human T cell function.Eur J Immun 10, 758 (1980).
Reinherz E L, Meuer S C, Fitzgerald K A, Hussey R E, Levine H, Schlossman S F: Antigen recognition by human T lymphocytes is linked to surface expression of the T3 molecular complex.Cell 30, 735 (1982).
Reinherz E L, Meuer S C, Fitzgerald K A, Hussey R E, Hodgdon J C, Acuto O, Schlossman S F: Comparison of T3 associated 49- and 43-kilodalton cell surface molecules on individual human T-cell clones: evidence for peptide variability in T-cell receptor structures.Proc Natn Acad Sci USA 80, 4104 (1983).
Acuto O, Fabbi M, Smart J, Poole C B, Protentis J, Royer H D, Schlossman S F, Reinherz E L:Proc Natn Acad Sci USA (in press).
Yanagi Y, Yoshikai Y, Leggett K, Clark S P, Aleksander I, Mak T W: A human T cell specific cDNA clone encodes a protein having extensive homology to immunoglobulin chains.Nature 308, 145 (1984).
Hedrick S M, Cohen D I, Nielsen E A, Davis M M: Isolation of cDNA clones encoding T cell-specific membrane associated proteins.Nature 308, 149 (1984).
Hedrick S M, Nielsen E A, Kavaler J, Cohen D I, Davis M M: Sequence relationships between putative T-cell receptor polypeptides and immunoglobulins.Nature 308, 153 (1984).
Meuer S C, Hodgdon J C, Hussey R E, Protentis J P, Schlossman S F, Reinherz E L: Antigen-like effects of monoclonal antibodies directed at receptors on human T cell clones.J Exp Med 158, 988 (1983).
Meuer S C, Hussey R E, Cantrell D A, Schlossman S F, Smith K A, Reinherz E L: Triggering of the T3-T1 antigen-receptor complex results in clonal T cell proliferation through an interleukin-2-dependent autocrine pathway.Proc Natn Acad Sci USA 81, 1509 (1984).
Romain P L, Morimoto C, Daley J F, Palley L S, Reinherz E L, Schlossman S F: Reactivity of inducer cell subsets and T8-cell activation during the human autologous mixed lymphocyte reaction.Clin Immun Immunopath 30, 117 (1984).
Reinherz E L, Morimoto C, Penta A C, Schlossman S F: Regulation of B cell immunoglobulin secretion by functional subsets of T lymphocytes in man.Eur J Immun 10, 570 (1980).
Morimoto C, Reinherz E L, Schlossman S F: Regulation ofin vitro primary anti-DNP antibody production by functional subsets of T lymphocytes in man.J Immun 127, 69 (1981).
Reinherz E L, Kung P C, Breard J M, Goldstein G, Schlossman S F: T cell requirements for generation of helper factor(s) in man: analysis of the subsets involved.J Immun 124, 1883 (1980).
Morimoto C, Reinherz E L, Borel Y, Mantzouranis E, Steinberg A D, Schlossman S F: Autoantibody to an immunoregulatory inducer population in patients with juvenile rheumatoid arthritis.J Clin Invest 67, 753 (1981).
Meuer S C, Hussey R E, Penta A C, Fitzgerald K A, Stadler B M, Schlossman S F, Reinherz E L: Cellular origin of interleukin 2 (IL 2) in man: evidence for stimulus-restricted IL 2 production by T4+ and T8+ T lymphocytes.J Immun 129, 1076 (1982).
Reinherz E L, Morimoto C, Fitzgerald K A, Hussey R E, Daley J F, Schlossman S F: Heterogeneity of human T4+ inducer T cells defined by a monoclonal antibody that delineates two functional subpopulations.J Immun 128, 463 (1982).
Morimoto C, Distaso J A, Borel Y, Schlossman S F, Reinherz E L: Communicative interactions between subpopulations of human T lymphocytes required for generation of suppressor effector function in a primary antibody response.J Immun 128, 1645 (1982).
Morimoto C, Masuho Y, Borel Y, Steinberg A D, Schlossman S F: Selective inhibition of anti-nucleoside-specific antibody production by nucleoside-ricin A conjugate.J Immun 131, 1762 (1983).
Morimoto C, Reinherz E L, Borel Y, Schlossman S F: Direct demonstration of the human suppressor inducer subset by anti-T cell antibodies.J Immun 130, 157 (1983).
Reinherz E L, Morimoto C, Penta A C, Schlossman S F: Subpopulations of the T4+ inducer T cell subset in man: evidence for an amplifier population preferentially expressing Ia antigen upon activation.J Immun 126, 67 (1981).
Meuer S C, Cooper D A, Hodgdon J C, Hussey R E, Morimoto C, Schlossman S F, Reinherz E L: Immunoregulatory human T lymphocytes triggered as a consequence of viral infection: clonal analysis of helper, suppressor inducer and suppressor effector cell populations.J Immun 131, 1167 (1983).
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Schlossman, S.F. Dissection of the T-cell circuit with monoclonal antibodies. Med. Oncol. & Tumor Pharmacother. 1, 247–253 (1984). https://doi.org/10.1007/BF02934530
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DOI: https://doi.org/10.1007/BF02934530