Skip to main content
NCBI home page
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1985 May 1;161(5):1063–1078. doi: 10.1084/jem.161.5.1063

TLiSA1, a human T lineage-specific activation antigen involved in the differentiation of cytotoxic T lymphocytes and anomalous killer cells from their precursors

PMCID: PMC2187589  PMID: 2580933

Abstract

The characteristics of a novel T lineage-specific activation antigen, termed TLiSA1, are described. The antigen was detected with a mouse monoclonal antibody, LeoA1, that was raised against activated human T cells generated in mixed lymphocyte culture (MLC). The antigen became strongly expressed on T cells 48-72 h after stimulation with phytohemagglutinin, and retained expression on MLC-activated T cells after 10 d of culture. The antigen was absent from a range of human T, B, myeloid, fibroblast, and tumour cell lines, but was present on the surface of the interleukin 2 (IL-2)-dependent gibbon cell line MLA-144. Analysis of the antigen by sodium dodecyl sulfate-polyacrylamide gel electrophoresis of immunoprecipitates obtained from activated human T cells demonstrated a broad band in the region of 70 kD, whereas precipitates obtained from MLA-144 revealed a single narrow band of 95 kD. The molecule was expressed with a maximum density of 66,000 copies per cell on the surface of MLC-activated T cell blasts, as assessed by Scatchard analysis. TLiSA1 was distinguished from the IL-2 receptor bound by the anti-Tac monoclonal antibody by demonstrating that the antigens did not comodulate or coprecipitate, and by constructing an IL- 2-independent human T X T hybrid that expressed the TLiSA1 but not the Tac antigen. MLC with B lymphoblasts was used to generate cytotoxic T lymphocytes (CTL) specific for the stimulating cell, and anomalous killer (AK) cells able to kill melanoma target cells. The presence of LeoA1 or F(ab')2 fragments of the antibody from the beginning of coculture did not affect proliferation in these cultures, but did inhibit the induction of both CTL and AK cells from their precursors. This inhibition of differentiation by LeoA1 was confirmed under conditions of limiting dilution, where it was shown that the antibody reduced the frequency of CTL produced, and greatly (fourfold) reduced the frequency of AK cells generated from their precursors. We discuss the possibility that human CTL may express a differentiation factor receptor that is distinct from the receptor for IL-2.

Full Text

The Full Text of this article is available as a PDF (1.1 MB).

Selected References

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

  1. Brooks C. G., Urdal D. L., Henney C. S. Lymphokine-driven "differentiation" of cytotoxic T-cell clones into cells with NK-like specificity: correlations with display of membrane macromolecules. Immunol Rev. 1983;72:43–72. doi: 10.1111/j.1600-065x.1983.tb01072.x. [DOI] [PubMed] [Google Scholar]
  2. Burns G. F., Boyd A. W., Beverley P. C. Two monoclonal anti-human T lymphocyte antibodies have similar biologic effects and recognize the same cell surface antigen. J Immunol. 1982 Oct;129(4):1451–1457. [PubMed] [Google Scholar]
  3. Burns G. F., Good M. F., Riglar C., Bartlett P. F., Crapper R. M., Mackay I. R. Activated lymphocyte killer cells derived from melanoma tissue or peripheral blood. Clin Exp Immunol. 1984 Aug;57(2):487–494. [PMC free article] [PubMed] [Google Scholar]
  4. Burns G. F., Triglia T., Bartlett P. F., Mackay I. R. Human natural killer cells, activated lymphocyte killer cells, and monocytes possess similar cytotoxic mechanisms. Proc Natl Acad Sci U S A. 1983 Dec;80(24):7606–7610. doi: 10.1073/pnas.80.24.7606. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Burns G. F., Triglia T., Werkmeister J. A. In vitro generation of human activated lymphocyte killer cells: separate precursors and modes of generation of NK-like cells and "anomalous" killer cells. J Immunol. 1984 Sep;133(3):1656–1663. [PubMed] [Google Scholar]
  6. Burns G. F., Werkmeister J. A., Triglia T. A novel antigenic cell surface protein associated with T200 is involved in the post-activation stage of human NK cell-mediated lysis. J Immunol. 1984 Sep;133(3):1391–1396. [PubMed] [Google Scholar]
  7. Burns G. F., Werkmeister J. A., Triglia T. High frequency of precursors of anomalous killer cells in human peripheral blood: evidence for T-cell regulation. Cell Immunol. 1984 Nov;89(1):202–211. doi: 10.1016/0008-8749(84)90210-7. [DOI] [PubMed] [Google Scholar]
  8. Cooper J., Eichmann K., Fey K., Melchers I., Simon M. M., Weltzien H. U. Network regulation among T cells: qualitative and quantitative studies on suppression in the non-immune state. Immunol Rev. 1984 Jun;79:63–86. doi: 10.1111/j.1600-065x.1984.tb00487.x. [DOI] [PubMed] [Google Scholar]
  9. Cotner T., Williams J. M., Christenson L., Shapiro H. M., Strom T. B., Strominger J. Simultaneous flow cytometric analysis of human T cell activation antigen expression and DNA content. J Exp Med. 1983 Feb 1;157(2):461–472. doi: 10.1084/jem.157.2.461. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Depper J. M., Leonard W. J., Krönke M., Waldmann T. A., Greene W. C. Augmented T cell growth factor receptor expression in HTLV-1-infected human leukemic T cells. J Immunol. 1984 Oct;133(4):1691–1695. [PubMed] [Google Scholar]
  11. Depper J. M., Leonard W. J., Robb R. J., Waldmann T. A., Greene W. C. Blockade of the interleukin-2 receptor by anti-Tac antibody: inhibition of human lymphocyte activation. J Immunol. 1983 Aug;131(2):690–696. [PubMed] [Google Scholar]
  12. Erard F., Corthesy P., Smith K. A., Fiers W., Conzelmann A., Nabholz M. Characterization of soluble factors that induce the cytolytic activity and the expression of T cell growth factor receptors of a T cell hybrid. J Exp Med. 1984 Aug 1;160(2):584–599. doi: 10.1084/jem.160.2.584. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Finke J. H., Scott J., Gillis S., Hilfiker M. L. Generation of alloreactive cytotoxic T lymphocytes: evidence for a differentiation factor distinct from IL 2. J Immunol. 1983 Feb;130(2):763–767. [PubMed] [Google Scholar]
  14. Fox D. A., Hussey R. E., Fitzgerald K. A., Acuto O., Poole C., Palley L., Daley J. F., Schlossman S. F., Reinherz E. L. Ta1, a novel 105 KD human T cell activation antigen defined by a monoclonal antibody. J Immunol. 1984 Sep;133(3):1250–1256. [PubMed] [Google Scholar]
  15. Fox D. A., Hussey R. E., Fitzgerald K. A., Bensussan A., Daley J. F., Schlossman S. F., Reinherz E. L. Activation of human thymocytes via the 50KD T11 sheep erythrocyte binding protein induces the expression of interleukin 2 receptors on both T3+ and T3- populations. J Immunol. 1985 Jan;134(1):330–335. [PubMed] [Google Scholar]
  16. Goding J. W., Burns G. F. Monoclonal antibody OKT-9 recognizes the receptor for transferrin on human acute lymphocytic leukemia cells. J Immunol. 1981 Sep;127(3):1256–1258. [PubMed] [Google Scholar]
  17. 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]
  18. Hercend T., Ritz J., Schlossman S. F., Reinherz E. L. Comparative expression of T9, T10, and Ia antigens on activated human T cell subsets. Hum Immunol. 1981 Nov;3(3):247–259. doi: 10.1016/0198-8859(81)90021-5. [DOI] [PubMed] [Google Scholar]
  19. Jondal M., Targan S. In vitro induction of cytotoxic effector cells with spontaneous killer cell specificity. J Exp Med. 1978 Jun 1;147(6):1621–1636. doi: 10.1084/jem.147.6.1621. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Lazarovits A. I., Moscicki R. A., Kurnick J. T., Camerini D., Bhan A. K., Baird L. G., Erikson M., Colvin R. B. Lymphocyte activation antigens. I. A monoclonal antibody, anti-Act I, defines a new late lymphocyte activation antigen. J Immunol. 1984 Oct;133(4):1857–1862. [PubMed] [Google Scholar]
  21. Leonard W. J., Depper J. M., Uchiyama T., Smith K. A., Waldmann T. A., Greene W. C. A monoclonal antibody that appears to recognize the receptor for human T-cell growth factor; partial characterization of the receptor. Nature. 1982 Nov 18;300(5889):267–269. doi: 10.1038/300267a0. [DOI] [PubMed] [Google Scholar]
  22. MacDonald H. R., Lees R. K. Dissociation of differentiation and proliferation in the primary induction of cytolytic T lymphocytes by alloantigens. J Immunol. 1980 Mar;124(3):1308–1313. [PubMed] [Google Scholar]
  23. Merluzzi V. J., Savage D. M., Mertelsmann R., Welte K. Generation of nonspecific murine cytotoxic T cells in vitro by purified human interleukin 2. Cell Immunol. 1984 Mar;84(1):74–84. doi: 10.1016/0008-8749(84)90078-9. [DOI] [PubMed] [Google Scholar]
  24. 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. 1984 Apr;36(4):897–906. doi: 10.1016/0092-8674(84)90039-4. [DOI] [PubMed] [Google Scholar]
  25. Miyawaki T., Yachie A., Uwadana N., Ohzeki S., Nagaoki T., Taniguchi N. Functional significance of Tac antigen expressed on activated human T lymphocytes: Tac antigen interacts with T cell growth factor in cellular proliferation. J Immunol. 1982 Dec;129(6):2474–2478. [PubMed] [Google Scholar]
  26. Parham P. On the fragmentation of monoclonal IgG1, IgG2a, and IgG2b from BALB/c mice. J Immunol. 1983 Dec;131(6):2895–2902. [PubMed] [Google Scholar]
  27. Peters P. M., Kamarck M. E., Hemler M. E., Strominger J. L., Ruddle F. H. Genetic and biochemical characterization of human lymphocyte cell surface antigens. The A-1A5 and A-3A4 determinants. J Exp Med. 1984 May 1;159(5):1441–1454. doi: 10.1084/jem.159.5.1441. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Rabin H., Hopkins R. F., 3rd, Ruscetti F. W., Neubauer R. H., Brown R. L., Kawakami T. G. Spontaneous release of a factor with properties of T cell growth factor from a continuous line of primate tumor T cells. J Immunol. 1981 Nov;127(5):1852–1856. [PubMed] [Google Scholar]
  29. Raulet D. H., Bevan M. J. A differentiation factor required for the expression of cytotoxic T-cell function. Nature. 1982 Apr 22;296(5859):754–757. doi: 10.1038/296754a0. [DOI] [PubMed] [Google Scholar]
  30. Seeley J. K., Golub S. H. Studies on cytotoxicity generated in human mixed lymphocyte cultures. I. Time course and target spectrum of several distinct concomitant cytotoxic activities. J Immunol. 1978 Apr;120(4):1415–1422. [PubMed] [Google Scholar]
  31. Shortman K., Wilson A., Scollay R., Chen W. F. Development of large granular lymphocytes with anomalous, nonspecific cytotoxicity in clones derived from Ly-2+ T cells. Proc Natl Acad Sci U S A. 1983 May;80(9):2728–2732. doi: 10.1073/pnas.80.9.2728. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Shortman K., Wilson A., Scollay R. Loss of specificity in cytolytic T lymphocyte clones obtained by limit dilution culture of Ly-2+ T cells. J Immunol. 1984 Feb;132(2):584–593. [PubMed] [Google Scholar]
  33. Triglia T., Burns G. F. A method for in vitro clearance of mycoplasma from human cell lines. J Immunol Methods. 1983 Nov 11;64(1-2):133–139. doi: 10.1016/0022-1759(83)90391-5. [DOI] [PubMed] [Google Scholar]
  34. Tsudo M., Uchiyama T., Uchino H. Expression of Tac antigen on activated normal human B cells. J Exp Med. 1984 Aug 1;160(2):612–617. doi: 10.1084/jem.160.2.612. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Uchiyama T., Broder S., Waldmann T. A. A monoclonal antibody (anti-Tac) reactive with activated and functionally mature human T cells. I. Production of anti-Tac monoclonal antibody and distribution of Tac (+) cells. J Immunol. 1981 Apr;126(4):1393–1397. [PubMed] [Google Scholar]
  36. Wagner H., Hardt C., Rouse B. T., Röllinghoff M., Scheurich P., Pfizenmaier K. Dissection of the proliferative and differentiative signals controlling murine cytotoxic T lymphocyte responses. J Exp Med. 1982 Jun 1;155(6):1876–1881. doi: 10.1084/jem.155.6.1876. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Watson D. B., Burns G. F., Mackay I. R. In vitro growth of B lymphocytes infiltrating human melanoma tissue by transformation with EBV: evidence for secretion of anti-melanoma antibodies by some transformed cells. J Immunol. 1983 May;130(5):2442–2447. [PubMed] [Google Scholar]
  38. Yssel H., Spits H., de Vries J. E. A cloned human T cell line cytotoxic for autologous and allogeneic B lymphoma cells. J Exp Med. 1984 Jul 1;160(1):239–254. doi: 10.1084/jem.160.1.239. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. van de Griend R. J., Giphart M. J., Van Krimpen B. A., Bolhuis R. L. Human T cell clones exerting multiple cytolytic activities show heterogeneity in susceptibility to inhibition by monoclonal antibodies. J Immunol. 1984 Sep;133(3):1222–1229. [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES