Abstract
The induction of a T-cell immune response to a foreign antigen requires the activation of T lymphocytes with receptors for the specific antigen. The human antigen-specific T-cell receptor has been shown to be a polymorphic heterodimer of α and β chains of approximately 40–50 Kd associated with three or four 20- to 28-Kd nonpolymorphic polypeptide chains identified by the T3 monoclonal antibody (1–6). T-cell activation is initiated following the interaction of antigens, mitogens, or antibodies with this complex antigen-specific T-cell receptor. First, after the interaction with antigen presented in the context of products of a major histocompatibility locus and the macrophage-derived interleukin-1, T cells express the gene encoding the lymphokine interleukin-2 (IL-2), previously termed T-cell growth factor (7,8). To exert its biological effect, IL-2 must interact with specific high-affinity membrane receptors. Resting T cells do not express IL-2 receptors, but receptors are rapidly expressed on T cells after activation with an antigen or mitogen (9–11). Thus, but after activation the genes for both proteins become expressed. A failure of the production of either the growth factor or its receptor results in failure of the T-cell immune response. Thus, both the production of IL-2 and the display of IL-2 receptors are pivotal events in the full expression of the T-cell immune response. Although the interaction of appropriately presented antigen with its specific polymorphic receptor complex confers specificity for a given immune response, the interaction of IL-2 with IL-2 receptors determines its magnitude and duration.
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References
J. P. Allison, B. W. Mclntyre and D. Bloch. Tumor-specific antigen of murine T lymphoma defined with monoclonal antibody. J. Immunol. 129:2293, (1982).
K. Haskins, R. Kubo, J. White, M. Pigeon, J. Kappler, and P. Marrack. The major histocompatibility complex-restricted antigen receptor on T cells. Isolation with a monoclonal antibody. J. Exp. Med. 157:1149, (1983).
S. C. Meuer, K. A. Fitzgerald, R. E. Hussey, J. C. Hodgdon, S. F. Schlossman, and E. L. Reinherz. Clonotypic structures involved in antigen-specific human T cell function. J. Exp. Med. 157:705, (1985).
S. M. Hedrick, D. I. Cohen, E. A. Nielsen, and M. M. Davis. Isolation of cDNA clones encoding T-cell specific membrane-associated proteins. Nature 308:149, (1984).
Y. Yanagi, Y. Yoshikai, R. Leggett, S. P. Clark, I. Alexander, and T. W. Mak. A human T-cell specific cDNA clone encodes a protein having extensive homology to immunoglobulin chains. Nature 308:145, (1984).
J. Borst, S. Alexander, J. Elder, and C. Terhost. The T3 complex on human T lymphocytes involves four structurally distinct glycoproteins. J. Biol. Chem. 258:5153, (1983).
D. A. Morgan, F. W. Ruscetti, and R. C. Gallo. Selective in vitro growth of T lymphocytes from normal human bone marrows. Science 193:1007, 1976.
K. A. Smith. T-cell growth factor. Immuno. Rev. 51:337, (1980).
R. J. Robb, A. Munck, and K. A. Smith. T-cell growth factors: quantification, specificity, and biological relevance. J. Exp. Med. 154:1455, (1981).
W. C. Greene, W. J. Leonard, and J. M. Depper. Growth of human T lymphocytes: an analysis of IL-2 and the IL-2 receptor. In Progress in Hematology, Vol XIV, E. Brown (ed), Grune and Stratton, New York, (1985) p 283.
T. A. Waldmann. The structure, function, and expression of interleukin-2 receptors on normal and malignant T cells. Science, in press.
T. Uchiyama, S. Broder, and T. A. Waldmann. A monoclonal antibody (anti-Tac) reactive with activated and functionally mature human T cells. J. Immunol. 126:1393, (1983).
W. J. Leonard, J. M. Depper, T. Uchiyama, K. A. Smith, T. A. Waldmann, and W. C. Greene. A monoclonal antibody that appears to recognize the receptor for human T cell growth factor: partial characterization of the receptor. Nature 300:267, (1982).
W. J. Leonard, J. M. Depper, R. J. Robb, T. A. Waldmann, and W. C. Greene. Characterization of the human receptor for T cell growth factor. Proc. Natl. Acad. Sci. USA 80:6957. (1983).
R. J. Robb, and W. C. Greene. Direct demonstration of the identity of T-cell growth factor binding protein and the Tac antigen. J. Exp. Med. 158:1332, (1983).
J. M. Depper, W. J. Leonard, M. Kronke, T. A. Waldmann, and W. C. Greene. Augmentation of T-cell growth factor expression in HTLV-I-infected human leukemic T cells. J. Immunol. 133:1691, (1984).
J. M. Depper, W. J. Leonard, M. Kironke, P. Noguchi, R. Cunningham, T. A. Waldmann, and W. C. Greene. Regulation of interleukin-2 receptor expression: effects of phorbol diester, phospholipase C, and reexposure to lectin and antigen. J. Immunol. 133:3054, (1984).
R. J. Robb, W. C. Greene, and C. M. Rusk. Low and high affinity cellular receptors for interleukin 2: implications for the level of Tac antigen. J. Exp. Med. 160:1126, (1984).
W. J. Leonard, J. M. Depper, T. A. Waldmann, and W. C. Greene. A monoclonal antibody to the human receptor for T cell growth factor. In Receptors and Recognition, Vol 17, M Greaves (ed), Chapman & Hall, London, (1984) p 45.
D. A. Shackelford, and I. S. Trowbridge. Induction of expression and phosphorylation of the human interleukin 2 receptor by a phorbol diester. J. Biol. Chem. 259:11706. (1984).
W. J. Leonard, J. M. Depper, G. R. Crabtree, S. Rudikoff, J. Pumphrey, R. J. Robb, M. Kronke, P. B. Svetlik, N. J. Pefffer, T. A. Waldmann, and W. C. Greene. Molecular cloning and expression of cDNAs for the human interleukin-2 receptor. Nature 311:626, (1984).
W. J. Leonard, J. M. Depper, M. Kronke, N. J. Peffer, P. B. Svetlik, M. Sullivan, and W. C. Greene. Structure of the human interleukin-2 gene. Science 230:633, (1985).
T. A. Waldmann, C. K. Goldman, R. J. Robb, J. M. Depper, W. J. Leonard, S. O. Sharrow, K. F. Bongiovanni, S. J. Korsmeyer, and W. C. Greene. Expression of interleukin 2 receptors on activated human B cells. J. Exp. Med. 160:1450, (1984).
M. Tsudo, T. Uchiyama, and H. Uchino. Expression of Tac antigen on activated normal human B cells. J. Exp. Med. 160:612, (1984).
F. Herrmann, S. A. Cannistra, H. Levine, and J. D. Griffin. Expression of interleukin 2 by gamma interferon induced human leukemic and normal leukemic and normal monocyte cells. J. Exp. Med. 162:1111, (1985).
L. A. Rubin, C. C. Kurman, W. E. Biddison, N. D. Goldman, and D. L. Nelson. A monoclonal antibody 7G7/B6 binds to an epitope on the human interleukin-2 (IL-2) receptor that is distinct from that recognized by IL-2 or anti-Tac. Hvbridoma 4:91, (1985).
J. M. Depper, W. J. Leonard, T. A. Waldmann, and W. C. Greene. Blockade of the interleukin-2 receptor by anti-Tac antibody: inhibition of human lymphocyte activation. J. Immunol. 131:690. (1983).
M. T. Tsudo, K. Uchiyama, Takatsuki, H. Uchino, and J. Yodoi. Modulation of Tac antigen on activated human T cells by anti-Tac monoclonal antibody. J. Immunol. 129:592, (1982).
L. M. Neckers, and J. Cossman. Transferrin receptor induction in mitogen-stimulated human T lymphocytes is required for DNA synthesis and cell division and is regulated by interleukin 2. Proc. Natl. Acad. Sci. USA 80:3494, (1983).
T. Cotner, J. M. Williams, L. Christenson, H. M. Shapiro, T. B. Strom, and J. Strominger. Simultaneous flow cytometric analysis of human T cell activation antigen expression and DNA content. J. Exp. Med. 157:461, (1983).
T. A. Waldmann, W. C. Greene, P. S. Sarin, C. Saxinger, W. Blayney, W. A. Blattner, C. K. Goldman, K. Bongiovanni, S. Sharrow, J. M. Depper, W. Leonard, T. Uchiyama, and R. C. Gallo. Functional and phenotypic comparison of human T cell leukemia/lymphoma virus positive adult T cell leukemia with human T cell leukemia/lymphoma virus negative Sezary leukemia. J. Clin. Invest. 73:1711, (1984).
K. Takiasuki, T. Uchiyama, K. Sagawa, and J. Yodoi. Adult T cell leukemia in Japan. In topics in Hematology, S. Seno, F. Takiaku, S. Irino (eds), Excerpta Medica, Amsterdam (1977), p 73.
B. J. Poiesz, F. W. Ruscetti, A. F. Gazdar, P. A. Bunn, J. D. Minna, and R. C. Gallo. Detection and isolation of type C retrovirus particles from fresh and cultured lymphocytes of a patient with cutaneous T-cell lymphoma. Proc. Natl. Acad. Sci. USA 77:7415. (1980).
Y. Wano, T. Uchiyama, K. Fukui, M. Maeda, H. Uchino, and J. Yodoi. characterization of human interleukin 2 receptor (Tac expression) in normal and leukemic T cells: coexpression of normal and aberrant receptors in HUT 102 cells. J. Immunol. 132:3005, (1984).
M. Tsudo, T. Uchiyama, H. Uchino, and J. Yodoi. Failure of regulation of Tac antigen/TCGF receptor on adult T cell leukemia cells by anti-Tac monoclonal antibody. Blood 61:1014. (1983).
T. Uchiyama, Y. Wano, M. Tsudo, H. Umadome, T. Hori, S. Tamori, J. Yodoi, M. Maeda, N. Koboyshi, and M. Hatanaka. Abnormal Expression of Interleukin-2 Receptor (Tac Antigen) in Adult T-cell Leukemia. In. Retroviruses in Human Lymphoma/Leukemia: The Fifteenth International Symposium of the Princess Takamatsu Cancer Research Fund, M. Miwa (ed), Japan Sci. Soc. Press, Tokyo, (1985) p 253.
M. Seiki, S. Hattori, Y. Hirayama, and M. Yoshida. Human adult T-cell leukemia virus: Complete nucleotide sequence of the provirus genome integrated in leukemia cell DNA. Proc. Natl. Acad. Sci. USA 80:3618. (1983).
J. G. Sodroski, C. A. Rosen, and W. A. Haseltine. Trans-acting transcriptional activation of the long terminal repeat of human T lymphotrophic viruses in infected cells. Science 225:381, (1984).
T. A. Waldmann, D. L. Longo, W. J. Leonard, J. M. Depper, C. B. Thompson, M. Kronke, C. K. Goldman, S. Sharrow, K. Bongiovanni, and W. C. Greene. Interleukin-2 receptor (Tac antigen) expression in HTLV-I associated adult T-cell leukemia. Cancer Res. 45:4559. (1985).
M. Kronke, J. M. Depper, W. J. Leonard, E. S. Vitetta, T. A. Waldmann, and W. C. Greene. Anti-Tac-ricin A conjugates selectively inhibit protein synthesis in human T cell leukemia/lymphoma virus infected leukemic T cells. Blood 65:1416, (1985).
D. FitzGerald, T. A. Waldmann, M. C. Willingham, and I. Paston. Pseudomonas exotoxin-anti-Tac: cell specific immunotoxin, active against cells expressing the T-cell growth factor receptor. J. Clin. Invest. 784:966, (1984).
R. W. Kozak, R. W. Atcher, O. A. Gansow, A. M. Friedman, and T. A. Waldmann. Bismuth-212 labeled anti-Tac monoclonal antibody: alpha-particle emitting radionuclides as novel modalities for radioimmunotherapy. Proc. Natl. Acad. Sci. USA 83:474, (1986).
T. B. Strom, L. V. Banet, G. M. Gauiton, V. F. Kelley, A. Y. Thier, T. Diamanstein, N. L. Tilney, and R. L. Kirkman. Prolongation of cardiac allograft survival in rodent recipients treated with an anti-interleukin-2 receptor monoclonal antibody. Cancer Res. 33:561 A. (1985).
M. C. Zoumbos, P. Gascon, J. Djeu, S. R. Trost, and N. Young. Circulating activated suppressor T lymphocytes in aplastic anemia. N. Engl. J. Med. 312:257, (1985).
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Waldmann, T.A. (1987). The Interleukin-2 Receptor on Normal and Malignant Lymphocytes. In: Gupta, S., Paul, W.E., Fauci, A.S. (eds) Mechanisms of Lymphocyte Activation and Immune Regulation. Advances in Experimental Medicine and Biology, vol 213. Springer, Boston, MA. https://doi.org/10.1007/978-1-4684-5323-2_13
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DOI: https://doi.org/10.1007/978-1-4684-5323-2_13
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