Skip to main content
NCBI home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1987 Jun;84(12):4205–4209. doi: 10.1073/pnas.84.12.4205

Functional characterization of an antigen involved in an early step of T-cell activation.

M E Cosulich, A Rubartelli, A Risso, F Cozzolino, A Bargellesi
PMCID: PMC305053  PMID: 3295878

Abstract

An activation antigen, identified by the monoclonal antibody MLR3, is described that is present on activated T lymphocytes and thymocytes but not on resting T lymphocytes. Immunoprecipitation of radiolabeled membranes from an activated T-cell line showed that the MLR3-binding molecule has a molecular size of 28-34 kDa. Immunofluorescence analysis showed that the appearance of the MLR3 antigen is an early event and precedes that of the interleukin 2 receptor both in T lymphocytes and thymocytes. The proliferative response of resting T cells to OKT3-Sepharose and interleukin 1 or accessory cells, but not the interleukin 2-dependent proliferation, was inhibited by the addition of MLR3 monoclonal antibodies. Similar results wer also obtained in an interleukin 1-dependent human thymocyte proliferation assay. In addition when MLR3-positive cells were cultured with purified interleukin 1, MLR3 surface antigen expression was not observed. Thus MLR3 monoclonal antibody appears to recognize an antigen involved in an early step of T-cell activation related to interleukin 1-dependent functions and on both T lymphocytes and thymocytes.

Full text

PDF
4205

Images in this article

4208Image
on p.4208

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Clayberger C., Dekruyff R. H., Cantor H. Immunoregulatory activities of autoreactive T cells: an I-A-specific T cell clone mediates both help and suppression of antibody responses. J Immunol. 1984 May;132(5):2237–2243. [PubMed] [Google Scholar]
  2. Corte G., Moretta L., Damiani G., Mingari M. C., Bargellesi A. Surface antigens specifically expressed by activated T cells in humans. Eur J Immunol. 1981 Feb;11(2):162–164. doi: 10.1002/eji.1830110220. [DOI] [PubMed] [Google Scholar]
  3. Cosulich M. E., Risso A., Canonica G. W., Bargellesi A. Functional characterization of a regulatory human T-cell subpopulation increasing during autologous MLR. Immunology. 1986 Feb;57(2):265–273. [PMC free article] [PubMed] [Google Scholar]
  4. Davis L., Lipsky P. E. Signals involved in T cell activation. I. Phorbol esters enhance responsiveness but cannot replace intact accessory cells in the induction of mitogen-stimulated T cell proliferation. J Immunol. 1985 Nov;135(5):2946–2952. [PubMed] [Google Scholar]
  5. DeFreitas E. C., Chesnut R. W., Grey H. M., Chiller J. M. Macrophage-dependent activation of antigen-specific T cells requires antigen and a soluble monokine. J Immunol. 1983 Jul;131(1):23–29. [PubMed] [Google Scholar]
  6. Dower S. K., Call S. M., Gillis S., Urdal D. L. Similarity between the interleukin 1 receptors on a murine T-lymphoma cell line and on a murine fibroblast cell line. Proc Natl Acad Sci U S A. 1986 Feb;83(4):1060–1064. doi: 10.1073/pnas.83.4.1060. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Dower S. K., Kronheim S. R., March C. J., Conlon P. J., Hopp T. P., Gillis S., Urdal D. L. Detection and characterization of high affinity plasma membrane receptors for human interleukin 1. J Exp Med. 1985 Aug 1;162(2):501–515. doi: 10.1084/jem.162.2.501. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Grossi C. E., Zicca A., Leprini A., Cadoni A., Pistoia V., Ferrarini M. Acid hydrolases as markers of maturation in B-cell chronic lymphocytic leukemia. Blood. 1982 Jul;60(1):220–227. [PubMed] [Google Scholar]
  9. Haynes B. F., Hemler M. E., Mann D. L., Eisenbarth G. S., Shelhamer J., Mostowski H. S., Thomas C. A., Strominger J. L., Fauci A. S. Characterization of a monoclonal antibody (4F2) that binds to human monocytes and to a subset of activated lymphocytes. J Immunol. 1981 Apr;126(4):1409–1414. [PubMed] [Google Scholar]
  10. Haynes B. F., Hemler M., Cotner T., Mann D. L., Eisenbarth G. S., Strominger J. L., Fauci A. S. Characterization of a monoclonal antibody (5E9) that defines a human cell surface antigen of cell activation. J Immunol. 1981 Jul;127(1):347–351. [PubMed] [Google Scholar]
  11. Haynes B. F., Mann D. L., Hemler M. E., Schroer J. A., Shelhamer J. H., Eisenbarth G. S., Strominger J. L., Thomas C. A., Mostowski H. S., Fauci A. S. Characterization of a monoclonal antibody that defines an immunoregulatory T cell subset for immunoglobulin synthesis in humans. Proc Natl Acad Sci U S A. 1980 May;77(5):2914–2918. doi: 10.1073/pnas.77.5.2914. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Helderman J. H., Strom T. B. Role of protein and RNA synthesis in the development of insulin binding sites on activated thymus-derived lymphocytes. J Biol Chem. 1979 Aug 10;254(15):7203–7207. [PubMed] [Google Scholar]
  13. Hünig T., Loos M., Schimpl A. The role of accessory cells in polyclonal T cell activation. I. Both induction of interleukin 2 production and of interleukin 2 responsiveness by concanavalin A are accessory cell dependent. Eur J Immunol. 1983 Jan;13(1):1–6. doi: 10.1002/eji.1830130103. [DOI] [PubMed] [Google Scholar]
  14. Kappler J., Kubo R., Haskins K., Hannum C., Marrack P., Pigeon M., McIntyre B., Allison J., Trowbridge I. The major histocompatibility complex-restricted antigen receptor on T cells in mouse and man: identification of constant and variable peptides. Cell. 1983 Nov;35(1):295–302. doi: 10.1016/0092-8674(83)90232-5. [DOI] [PubMed] [Google Scholar]
  15. Kelso A., Macdonald H. R. Precursor frequency analysis of lymphokine-secreting alloreactive T lymphocytes. Dissociation of subsets producing interleukin 2, macrophage-activating factor, and granulocyte-macrophage colony-stimulating factor on the basis of Lyt-2 phenotype. J Exp Med. 1982 Nov 1;156(5):1366–1379. doi: 10.1084/jem.156.5.1366. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  17. Landegren U., Andersson J., Wigzell H. Mechanism of T lymphocyte activation by OKT3 antibodies. A general model for T cell induction. Eur J Immunol. 1984 Apr;14(4):325–328. doi: 10.1002/eji.1830140409. [DOI] [PubMed] [Google Scholar]
  18. Larsson E. L., Iscove N. N., Coutinho A. Two distinct factors are required for induction of T-cell growth. Nature. 1980 Feb 14;283(5748):664–666. doi: 10.1038/283664a0. [DOI] [PubMed] [Google Scholar]
  19. Manger B., Weiss A., Weyand C., Goronzy J., Stobo J. D. T cell activation: differences in the signals required for IL 2 production by nonactivated and activated T cells. J Immunol. 1985 Dec;135(6):3669–3673. [PubMed] [Google Scholar]
  20. Marchalonis J. J., Cone R. E., Santer V. Enzymic iodination. A probe for accessible surface proteins of normal and neoplastic lymphocytes. Biochem J. 1971 Oct;124(5):921–927. doi: 10.1042/bj1240921. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Matsushima K., Akahoshi T., Yamada M., Furutani Y., Oppenheim J. J. Properties of a specific interleukin 1 (IL 1) receptor on human Epstein Barr virus-transformed B lymphocytes: identity of the receptor for IL 1-alpha and IL 1-beta. J Immunol. 1986 Jun 15;136(12):4496–4502. [PubMed] [Google Scholar]
  22. 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. 1983 Feb 1;157(2):705–719. doi: 10.1084/jem.157.2.705. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. 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. 1983 Sep 1;158(3):988–993. doi: 10.1084/jem.158.3.988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Meuer S. C., Hussey R. E., Cantrell D. A., Hodgdon J. C., Schlossman S. F., Smith K. A., Reinherz E. L. Triggering of the T3-Ti antigen-receptor complex results in clonal T-cell proliferation through an interleukin 2-dependent autocrine pathway. Proc Natl Acad Sci U S A. 1984 Mar;81(5):1509–1513. doi: 10.1073/pnas.81.5.1509. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Moore R. N., Oppenheim J. J., Farrar J. J., Carter C. S., Jr, Waheed A., Shadduck R. K. Production of lymphocyte-activating factor (Interleukin 1) by macrophages activated with colony-stimulating factors. J Immunol. 1980 Sep;125(3):1302–1305. [PubMed] [Google Scholar]
  26. Robb R. J., Greene W. C. Direct demonstration of the identity of T cell growth factor binding protein and the Tac antigen. J Exp Med. 1983 Oct 1;158(4):1332–1337. doi: 10.1084/jem.158.4.1332. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Robb R. J., Munck A., Smith K. A. T cell growth factor receptors. Quantitation, specificity, and biological relevance. J Exp Med. 1981 Nov 1;154(5):1455–1474. doi: 10.1084/jem.154.5.1455. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Roska A. K., Lipsky P. E. Dissection of the functions of antigen-presenting cells in the induction of T cell activation. J Immunol. 1985 Nov;135(5):2953–2961. [PubMed] [Google Scholar]
  29. Rubartelli A., Sitia R., Zicca A., Grossi C. E., Ferrarini M. Differentiation of chronic lymphocytic leukemia cells: correlation between the synthesis and secretion of immunoglobulins and the ultrastructure of the malignant cells. Blood. 1983 Aug;62(2):495–504. [PubMed] [Google Scholar]
  30. Schwab R., Crow M. K., Russo C., Weksler M. E. Requirements for T cell activation by OKT3 monoclonal antibody: role of modulation of T3 molecules and interleukin 1. J Immunol. 1985 Sep;135(3):1714–1718. [PubMed] [Google Scholar]
  31. Smith K. A. Interleukin 2. Annu Rev Immunol. 1984;2:319–333. doi: 10.1146/annurev.iy.02.040184.001535. [DOI] [PubMed] [Google Scholar]
  32. Smith K. A., Lachman L. B., Oppenheim J. J., Favata M. F. The functional relationship of the interleukins. J Exp Med. 1980 Jun 1;151(6):1551–1556. doi: 10.1084/jem.151.6.1551. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Sutherland R., Delia D., Schneider C., Newman R., Kemshead J., Greaves M. Ubiquitous cell-surface glycoprotein on tumor cells is proliferation-associated receptor for transferrin. Proc Natl Acad Sci U S A. 1981 Jul;78(7):4515–4519. doi: 10.1073/pnas.78.7.4515. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Tosi R., Tanigaki N., Sorrentino R., Accolla R., Corte G. Binding of one monoclonal antibody to human Ia molecules can be enhanced by a second monoclonal antibody. Eur J Immunol. 1981 Sep;11(9):721–726. doi: 10.1002/eji.1830110910. [DOI] [PubMed] [Google Scholar]
  35. Tsoukas C. D., Landgraf B., Bentin J., Valentine M., Lotz M., Vaughan J. H., Carson D. A. Activation of resting T lymphocytes by anti-CD3 (T3) antibodies in the absence of monocytes. J Immunol. 1985 Sep;135(3):1719–1723. [PubMed] [Google Scholar]
  36. Uchiyama T., Nelson D. L., Fleisher T. A., Waldmann T. A. A monoclonal antibody (anti-Tac) reactive with activated and functionally mature human T cells. II. Expression of Tac antigen on activated cytotoxic killer T cells, suppressor cells, and on one of two types of helper T cells. J Immunol. 1981 Apr;126(4):1398–1403. [PubMed] [Google Scholar]
  37. Williams J. M., Deloria D., Hansen J. A., Dinarello C. A., Loertscher R., Shapiro H. M., Strom T. B. The events of primary T cell activation can be staged by use of Sepharose-bound anti-T3 (64.1) monoclonal antibody and purified interleukin 1. J Immunol. 1985 Oct;135(4):2249–2255. [PubMed] [Google Scholar]
  38. Williams J. M., Ransil B. J., Shapiro H. M., Strom T. B. Accessory cell requirement for activation antigen expression and cell cycle progression by human T lymphocytes. J Immunol. 1984 Dec;133(6):2986–2995. [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES