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.
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- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]