Skip to main content
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1990 Oct 1;172(4):1071–1082. doi: 10.1084/jem.172.4.1071

T cell target 1 (TCT.1): a novel target molecule for human non-major histocompatibility complex-restricted T lymphocytes

PMCID: PMC2188610  PMID: 2212943

Abstract

We have studied two gamma/delta T cell clones, E102 and E117, generated in a mixed lymphocyte culture using an allogeneic Epstein-Barr virus- transformed B cell line, E418. These clones were both found to express a molecular form of T cell receptor (TCR) infrequent in human peripheral blood, associating a V1-J1-C delta chain and a V3-JP2-C2 gamma chain. Functionally, they appeared as cytotoxic T lymphocytes (CTL) with non-major histocompatibility complex (MHC) (class I and II) requiring cytotoxicity, able to kill both the immunizing (i.e., E418) and unrelated (e.g., K562, REX, F601, and KAS) target cells. A monoclonal antibody, anti-10H3, able to selectively inhibit the cytotoxic activity of the clones has been produced. This reagent defines a 43-kD molecule, designated TCT.1, with broad distribution in the hematopoietic system, that appears to be distinct from class I MHC gene products. A series of functional experiments using various effector/target cell combinations strongly suggested that TCT.1 may represent a unique TCR ligand involved in the interaction between these particular CTL clones and certain of the target cells tested, while others were likely to be recognized and killed through a TCR- independent natural killer-like pathway. Although further experimentation will be needed to strengthen our interpretation of the present data, this study provides additional evidence that some T lymphocytes, in particular of the gamma/delta type, may interact specifically with target cells in a non-MHC class I/II-requiring fashion.

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. Band H., Hochstenbach F., McLean J., Hata S., Krangel M. S., Brenner M. B. Immunochemical proof that a novel rearranging gene encodes the T cell receptor delta subunit. Science. 1987 Oct 30;238(4827):682–684. doi: 10.1126/science.3672118. [DOI] [PubMed] [Google Scholar]
  2. Bank I., DePinho R. A., Brenner M. B., Cassimeris J., Alt F. W., Chess L. A functional T3 molecule associated with a novel heterodimer on the surface of immature human thymocytes. Nature. 1986 Jul 10;322(6075):179–181. doi: 10.1038/322179a0. [DOI] [PubMed] [Google Scholar]
  3. Bluestone J. A., Cron R. Q., Cotterman M., Houlden B. A., Matis L. A. Structure and specificity of T cell receptor gamma/delta on major histocompatibility complex antigen-specific CD3+, CD4-, CD8- T lymphocytes. J Exp Med. 1988 Nov 1;168(5):1899–1916. doi: 10.1084/jem.168.5.1899. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Borst J., van de Griend R. J., van Oostveen J. W., Ang S. L., Melief C. J., Seidman J. G., Bolhuis R. L. A T-cell receptor gamma/CD3 complex found on cloned functional lymphocytes. Nature. 1987 Feb 19;325(6106):683–688. doi: 10.1038/325683a0. [DOI] [PubMed] [Google Scholar]
  5. Brenner M. B., McLean J., Scheft H., Riberdy J., Ang S. L., Seidman J. G., Devlin P., Krangel M. S. Two forms of the T-cell receptor gamma protein found on peripheral blood cytotoxic T lymphocytes. Nature. 1987 Feb 19;325(6106):689–694. doi: 10.1038/325689a0. [DOI] [PubMed] [Google Scholar]
  6. Brodsky F. M., Parham P. Monomorphic anti-HLA-A,B,C monoclonal antibodies detecting molecular subunits and combinatorial determinants. J Immunol. 1982 Jan;128(1):129–135. [PubMed] [Google Scholar]
  7. Casorati G., De Libero G., Lanzavecchia A., Migone N. Molecular analysis of human gamma/delta+ clones from thymus and peripheral blood. J Exp Med. 1989 Nov 1;170(5):1521–1535. doi: 10.1084/jem.170.5.1521. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Ciccone E., Viale O., Bottino C., Pende D., Migone N., Casorati G., Tambussi G., Moretta A., Moretta L. Antigen recognition by human T cell receptor gamma-positive lymphocytes. Specific lysis of allogeneic cells after activation in mixed lymphocyte culture. J Exp Med. 1988 Apr 1;167(4):1517–1522. doi: 10.1084/jem.167.4.1517. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Faure F., Jitsukawa S., Miossec C., Hercend T. CD1c as a target recognition structure for human T lymphocytes: analysis with peripheral blood gamma/delta cells. Eur J Immunol. 1990 Mar;20(3):703–706. doi: 10.1002/eji.1830200336. [DOI] [PubMed] [Google Scholar]
  10. Faure F., Jitsukawa S., Triebel F., Hercend T. Characterization of human peripheral lymphocytes expressing the CD3-gamma/delta complex with anti-receptor monoclonal antibodies. J Immunol. 1988 Nov 15;141(10):3357–3360. [PubMed] [Google Scholar]
  11. Faure F., Triebel F., Hercend T. MHC-unrestricted cytotoxicity. Immunol Today. 1990 Apr;11(4):108–110. doi: 10.1016/0167-5699(90)90041-7. [DOI] [PubMed] [Google Scholar]
  12. Feinberg A. P., Vogelstein B. A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem. 1983 Jul 1;132(1):6–13. doi: 10.1016/0003-2697(83)90418-9. [DOI] [PubMed] [Google Scholar]
  13. Fisch P., Malkovsky M., Braakman E., Sturm E., Bolhuis R. L., Prieve A., Sosman J. A., Lam V. A., Sondel P. M. Gamma/delta T cell clones and natural killer cell clones mediate distinct patterns of non-major histocompatibility complex-restricted cytolysis. J Exp Med. 1990 May 1;171(5):1567–1579. doi: 10.1084/jem.171.5.1567. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Haregewoin A., Soman G., Hom R. C., Finberg R. W. Human gamma delta+ T cells respond to mycobacterial heat-shock protein. Nature. 1989 Jul 27;340(6231):309–312. doi: 10.1038/340309a0. [DOI] [PubMed] [Google Scholar]
  15. 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]
  16. Hercend T., Meuer S., Brennan A., Edson M. A., Acuto O., Reinherz E. L., Schlossman S. F., Ritz J. Identification of a clonally restricted 90 kD heterodimer on two human cloned natural killer cell lines. Its role in cytotoxic effector function. J Exp Med. 1983 Nov 1;158(5):1547–1560. doi: 10.1084/jem.158.5.1547. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Hercend T., Reinherz E. L., Meuer S., Schlossman S. F., Ritz J. Phenotypic and functional heterogeneity of human cloned natural killer cell lines. Nature. 1983 Jan 13;301(5896):158–160. doi: 10.1038/301158a0. [DOI] [PubMed] [Google Scholar]
  18. Hercend T., Schmidt R., Brennan A., Edson M. A., Reinherz E. L., Schlossman S. F., Ritz J. Identification of a 140-kDa activation antigen as a target structure for a series of human cloned natural killer cell lines. Eur J Immunol. 1984 Sep;14(9):844–852. doi: 10.1002/eji.1830140914. [DOI] [PubMed] [Google Scholar]
  19. Holoshitz J., Koning F., Coligan J. E., De Bruyn J., Strober S. Isolation of CD4- CD8- mycobacteria-reactive T lymphocyte clones from rheumatoid arthritis synovial fluid. Nature. 1989 May 18;339(6221):226–229. doi: 10.1038/339226a0. [DOI] [PubMed] [Google Scholar]
  20. Janis E. M., Kaufmann S. H., Schwartz R. H., Pardoll D. M. Activation of gamma delta T cells in the primary immune response to Mycobacterium tuberculosis. Science. 1989 May 12;244(4905):713–716. doi: 10.1126/science.2524098. [DOI] [PubMed] [Google Scholar]
  21. Jitsukawa S., Faure F., Lipinski M., Triebel F., Hercend T. A novel subset of human lymphocytes with a T cell receptor-gamma complex. J Exp Med. 1987 Oct 1;166(4):1192–1197. doi: 10.1084/jem.166.4.1192. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Jitsukawa S., Triebel F., Faure F., Miossec C., Hercend T. Cloned CD3+ TcR alpha/beta- Ti gamma A- peripheral blood lymphocytes compared to the Ti gamma A+ counterparts: structural differences of the gamma/delta receptor and functional heterogeneity. Eur J Immunol. 1988 Nov;18(11):1671–1679. doi: 10.1002/eji.1830181104. [DOI] [PubMed] [Google Scholar]
  23. Koning F., Knot M., Wassenaar F., Van den Elsen P. Phenotypical heterogeneity among human T cell receptor gamma/delta-expressing clones derived from peripheral blood. Eur J Immunol. 1989 Nov;19(11):2099–2105. doi: 10.1002/eji.1830191120. [DOI] [PubMed] [Google Scholar]
  24. Kozbor D., Trinchieri G., Monos D. S., Isobe M., Russo G., Haney J. A., Zmijewski C., Croce C. M. Human TCR-gamma+/delta+, CD8+ T lymphocytes recognize tetanus toxoid in an MHC-restricted fashion. J Exp Med. 1989 May 1;169(5):1847–1851. doi: 10.1084/jem.169.5.1847. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. LeFranc M. P., Forster A., Baer R., Stinson M. A., Rabbitts T. H. Diversity and rearrangement of the human T cell rearranging gamma genes: nine germ-line variable genes belonging to two subgroups. Cell. 1986 Apr 25;45(2):237–246. doi: 10.1016/0092-8674(86)90388-0. [DOI] [PubMed] [Google Scholar]
  26. Mami-Chouaib F., Jitsukawa S., Faure F., Vasina B., Genevee C., Hercend T., Triebel F. cDNA cloning of functional T cell receptor gamma/delta chains expressed in human peripheral blood lymphocytes. Eur J Immunol. 1989 Sep;19(9):1545–1549. doi: 10.1002/eji.1830190905. [DOI] [PubMed] [Google Scholar]
  27. Matis L. A., Cron R., Bluestone J. A. Major histocompatibility complex-linked specificity of gamma delta receptor-bearing T lymphocytes. Nature. 1987 Nov 19;330(6145):262–264. doi: 10.1038/330262a0. [DOI] [PubMed] [Google Scholar]
  28. Matis L. A., Fry A. M., Cron R. Q., Cotterman M. M., Dick R. F., Bluestone J. A. Structure and specificity of a class II MHC alloreactive gamma delta T cell receptor heterodimer. Science. 1989 Aug 18;245(4919):746–749. doi: 10.1126/science.2528206. [DOI] [PubMed] [Google Scholar]
  29. Miossec C., Faure F., Ferradini L., Roman-Roman S., Jitsukawa S., Ferrini S., Moretta A., Triebel F., Hercend T. Further analysis of the T cell receptor gamma/delta+ peripheral lymphocyte subset. The V delta 1 gene segment is expressed with either C alpha or C delta. J Exp Med. 1990 Apr 1;171(4):1171–1188. doi: 10.1084/jem.171.4.1171. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Modlin R. L., Pirmez C., Hofman F. M., Torigian V., Uyemura K., Rea T. H., Bloom B. R., Brenner M. B. Lymphocytes bearing antigen-specific gamma delta T-cell receptors accumulate in human infectious disease lesions. Nature. 1989 Jun 15;339(6225):544–548. doi: 10.1038/339544a0. [DOI] [PubMed] [Google Scholar]
  31. Moingeon P., Jitsukawa S., Faure F., Troalen F., Triebel F., Graziani M., Forestier F., Bellet D., Bohuon C., Hercend T. A gamma-chain complex forms a functional receptor on cloned human lymphocytes with natural killer-like activity. Nature. 1987 Feb 19;325(6106):723–726. doi: 10.1038/325723a0. [DOI] [PubMed] [Google Scholar]
  32. O'Brien R. L., Happ M. P., Dallas A., Palmer E., Kubo R., Born W. K. Stimulation of a major subset of lymphocytes expressing T cell receptor gamma delta by an antigen derived from Mycobacterium tuberculosis. Cell. 1989 May 19;57(4):667–674. doi: 10.1016/0092-8674(89)90135-9. [DOI] [PubMed] [Google Scholar]
  33. Porcelli S., Brenner M. B., Greenstein J. L., Balk S. P., Terhorst C., Bleicher P. A. Recognition of cluster of differentiation 1 antigens by human CD4-CD8-cytolytic T lymphocytes. Nature. 1989 Oct 5;341(6241):447–450. doi: 10.1038/341447a0. [DOI] [PubMed] [Google Scholar]
  34. Quertermous T., Strauss W. M., Van Dongen J. J., Seidman J. G. Human T cell gamma chain joining regions and T cell development. J Immunol. 1987 Apr 15;138(8):2687–2690. [PubMed] [Google Scholar]
  35. Raulet D. H. Immunology. Antigens for gamma/delta T cells. Nature. 1989 Jun 1;339(6223):342–343. doi: 10.1038/339342a0. [DOI] [PubMed] [Google Scholar]
  36. Rimm I. J., Schlossman S. F., Reinherz E. L. Antibody-dependent cellular cytotoxicity and natural-killer-like activity are mediated by subsets of activated T cells. Clin Immunol Immunopathol. 1981 Oct;21(1):134–140. doi: 10.1016/0090-1229(81)90202-6. [DOI] [PubMed] [Google Scholar]
  37. Rivas A., Koide J., Cleary M. L., Engleman E. G. Evidence for involvement of the gamma, delta T cell antigen receptor in cytotoxicity mediated by human alloantigen-specific T cell clones. J Immunol. 1989 Mar 15;142(6):1840–1846. [PubMed] [Google Scholar]
  38. Seeley J. K., Masucci G., Poros A., Klein E., Golub S. H. Studies on cytotoxicity generated in human mixed lymphocyte cultures. II. Anti-K562 effectors are distinct from allospecific CTL and can be generated from NK-depleted T cells. J Immunol. 1979 Sep;123(3):1303–1311. [PubMed] [Google Scholar]
  39. Southern E. M. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol. 1975 Nov 5;98(3):503–517. doi: 10.1016/s0022-2836(75)80083-0. [DOI] [PubMed] [Google Scholar]
  40. Strominger J. L. The gamma delta T cell receptor and class Ib MHC-related proteins: enigmatic molecules of immune recognition. Cell. 1989 Jun 16;57(6):895–898. doi: 10.1016/0092-8674(89)90326-7. [DOI] [PubMed] [Google Scholar]
  41. Takihara Y., Reimann J., Michalopoulos E., Ciccone E., Moretta L., Mak T. W. Diversity and structure of human T cell receptor delta chain genes in peripheral blood gamma/delta-bearing T lymphocytes. J Exp Med. 1989 Feb 1;169(2):393–405. doi: 10.1084/jem.169.2.393. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Takihara Y., Tkachuk D., Michalopoulos E., Champagne E., Reimann J., Minden M., Mak T. W. Sequence and organization of the diversity, joining, and constant region genes of the human T-cell delta-chain locus. Proc Natl Acad Sci U S A. 1988 Aug;85(16):6097–6101. doi: 10.1073/pnas.85.16.6097. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Todd R. F., 3rd, Meuer S. C., Romain P. L., Schlossman S. F. A monoclonal antibody that blocks class II histocompatibility-related immune interactions. Hum Immunol. 1984 May;10(1):23–40. doi: 10.1016/0198-8859(84)90083-1. [DOI] [PubMed] [Google Scholar]
  44. Triebel F., Faure F., Graziani M., Jitsukawa S., Lefranc M. P., Hercend T. A unique V-J-C-rearranged gene encodes a gamma protein expressed on the majority of CD3+ T cell receptor-alpha/beta- circulating lymphocytes. J Exp Med. 1988 Feb 1;167(2):694–699. doi: 10.1084/jem.167.2.694. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Triebel F., Faure F., Mami-Chouaib F., Jitsukawa S., Griscelli A., Genevée C., Roman-Roman S., Hercend T. A novel human V delta gene expressed predominantly in the Ti gamma A fraction of gamma/delta+ peripheral lymphocytes. Eur J Immunol. 1988 Dec;18(12):2021–2027. doi: 10.1002/eji.1830181223. [DOI] [PubMed] [Google Scholar]
  46. Triebel F., Hercend T. Subpopulations of human peripheral T gamma delta lymphocytes. Immunol Today. 1989 Jun;10(6):186–188. doi: 10.1016/0167-5699(89)90321-6. [DOI] [PubMed] [Google Scholar]
  47. Vidović D., Roglić M., McKune K., Guerder S., MacKay C., Dembić Z. Qa-1 restricted recognition of foreign antigen by a gamma delta T-cell hybridoma. Nature. 1989 Aug 24;340(6235):646–650. doi: 10.1038/340646a0. [DOI] [PubMed] [Google Scholar]
  48. Wright A., Lee J. E., Link M. P., Smith S. D., Carroll W., Levy R., Clayberger C., Krensky A. M. Cytotoxic T lymphocytes specific for self tumor immunoglobulin express T cell receptor delta chain. J Exp Med. 1989 May 1;169(5):1557–1564. doi: 10.1084/jem.169.5.1557. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES