Abstract
T-cell clones expressing the γδ T-cell receptor (Tcr) were generated from peripheral blood lymphocytes (PBLs) and from a thymus sample. In the panel of ten thymus-derived clones, four γδ Tcr phenotypes [as defined by the reaction of monoclonal antibodies (mAbs) directed against known Vγ and Vδ regions] were identified. All the clones lacked expression of the Vδ3 V region, while seven clones were Vδ1+ . Vδ1 was found in combination with Vγ9 or with undefined VγVregions. In addition, two other γδ Tcr phenotypes were identified on these clones: Vγ9+ Vδ1− Vδ3− and Vγ9− Vγ1− Vγ3− One of the clones expressed CD4 and another was CD8positive. The remaining clones were CD4− CD8−. In the panel of 76 PBL-derived, γδ Tcr-bearing clones, five γδ Tcr phenotypes could be identified. In contrast to the thymus-derived clones, 30% of the clones were Vγ3+ whereas Vγ1 was expressed by a minority of the clones only. One clone was CD4-positive and approximately 30% of the clones were CD8-positive. Four of the five mAb-defined γδ Tcr phenotypes could be identified on both thymus and PBL-derived T-cell clones. However, biochemical analysis of the Tcrs demonstrates differences in the usage of Cγt- and Cγ2-encoded y chains by T cells derived from the thymus and PBLs. The results therefore indicate that, at the clonal level, similarities and differences exist between the γδ Tcr repertoires expressed in the thymus and by PBLs. Furthermore, they indicate that combinatorial γδ Tcr heterogeneity is larger than has so far been described. The receptor diversity, combined with the potential of γδ Tcr+ cells to express CD4 or CD8, indicates that these cells are a heterogeneous population that might mediate a number of immune functions.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Augustin, A., Kubo, R. T., and Sim, G.-K.: Resident pulmonary lymphocytes expressing the γ/δ T-cell receptor.Nature 340: 239–241, 1989
Band, H., Hochstenbach, F., McLean, J., Hata, M. S., Krangel, M. S., and Brenner, M. B.: Immunochemical proof that a novel rearranging gene encodes the T cell receptor γ subunit.Science 238: 682–684, 1987
Borst, J., van de Griend, R. J., van Oostveen, J. W., Ang, S.-L., Melief, C. J., Seidman, J. G., and Bolhuis, R. L. H.: A T-cell receptor γ/CD3 complex found on cloned functional lymphocytes.Nature 325: 683–688, 1987
Borst, J., van Dongen, J. J. M., Bolhuis, R. L. H., Peters, P. J., Hafler, D. A., de Vries, E., and van de Griend, R. J.: Distinct molecular forms of human T cell receptor γ/δ detected on viable T cells by a monoclonal antibody.J Exp Med 167: 1625–1644, 1988
Borst, J., Wicherink, A., van Dongen, J. J. M., de Vries, E., ComansBitter, W. M., Wassenaar, F., and van den Elsen, P.: Non-random expression of T cell receptor y and S variable gene segments in functional T lymphocyte clones from human peripheral blood.Eur J Immunol 19: 1559–1568, 1989
Bottino, C., Tambussi, G., Ferrini, S., Ciccone, E., Varese, P., Mingari, M. C., Moretta, L., and Moretta, A.: Two subsets of human T lymfocytes expressing γ/8 antigen receptor are identifiable by monoclonal antibodies directed to two distinct molecular forms of the receptor.J Exp Med 168: 491–505, 1988
Brenner, M. B., Mclean, J., Dialynas, D. P., Strominger, J. L., Smith, J. A., Owen, F. L., Seidman, J. G., Ip, S., Rosen, F., and Krangel, M. S.: Identification of a putative second T-cell receptor.Nature 322: 145–149, 1986
Brenner, M. B., Strominger, J. L., and Krangel, M. S.: The γδ T cell receptor.In F. J. Dixon (ed.):Advances in Immunology, Vol 43, pp. 133–192, Academic, London, 1988
Casorati, G., de Libero, G., Lanzavecchia, A., and Migone, N.: Molecular analysis of human γ/δ+ clones from thymus and peripheral blood.J Exp Med 170: 1521–1535, 1989
Ciccone, E., Ferinni, S., Bottino, C., Viale, O., Prigione, I., Pantaleo, G., Tambusi, G., Moretta, A., and Moretta, L.: A monoclonal antibody specific for a common determinant of the human T cell receptor γ/δ directly activates CD3+ WT31- lymphocytes to express their functional program(s).J Exp Med 168: 1–11, 1988
Elliott, J. F., Rock, E. P., Patten, P. A., Davis, M. M., and Chien, Y.: The adult T-cell receptor δ chain repertoire is diverse and distinct from that of fetal thymocytes.Nature 331: 627–631, 1988
Faure, F., Jitsukawa, S., Triebel, F., and Hercend, T.: Characterization of human peripheral lymfocytes expressing the CD3-γ/δ complex with anti-receptor monoclonal antibodies.J Immunol 141: 3357–3360, 1988
Goodman, T. and Lefrancois, L.: Expression of the γ-δ T-cell receptor on intestinal CD8+intraepithelial lymphocytes.Nature 333: 855–858, 1988
Groh, V., Porcelli, S., Fabbi, M., Lanier, L. L., Picker, L. J., Anderson, T., Warnke, R. A., Bhan, A. K., Strominger, J. L., and Brenner, M. B.: Human lymphocytes bearing T cell receptor γ/δ are phenotypically diverse and evenly distributed throughout the lymphoid system.J Exp Med 169: 1277–1294, 1989
Havran, W. L. and Allison, J. P.: Developmentally ordered appearance of thymocytes expressing different T-cell antigen receptors.Nature 335: 443–445, 1988
Hochstenbach, F., Parker, C., McLean, J., Gieselmann, V., Band, H., Bank, L., Chess, L., Spits, H., Strominger, J. L., Seidman, J. G., and Brenner, M. B.: Characterization of a third form of the human T cell receptor γ/δ.J Exp Med 168: 761–776, 1988
Holoshitz, J., Koning, F., Coligan, J. E., de Bruyn, J., and Strober, S.: Isolation of CD4−CD8− mycobacteria-reactive T lymphocyte clones from rheumatoid arthritis synovial fluid.Nature t339: 226–229, 1989
Jitsukawa, S., Faure, F., Lipinsky M., Triebel, F., and Hercend, T.: A novel subset of human lymfocytes with a T cell receptor-γ complex.J Exp Med 166: 1192–1197, 1987
Koning, F. and Coligan, J. E.: The γδ T Cell Receptor.In J. M. Cruse and R. E. Lewis (eds.):The Year in Immunology1988, pp. 94–109, Karger, Basel, 1989
Koning, F., Stingl, G., Yokoyama, W. M., Yamada, H., Maloy, W. L., Tschachler, E., Shevach, E. M., and Coligan, J. E.: Identification of a T3-associated γδ T cell receptor on Thy-1+ dendritic epidermal cell lines.Science 236: 834–837, 1987
Koning, F., Knot, M., Wassenaar, F., and van den Elsen, P.: Phenotypical heterogeneity among human T cell receptor γ/δ-expressing clones derived from peripheral blood.Eur J Immunol 19: 2099–2105, 1989
Kosbor, D., Trinchieri, G., Monos, D. S., Isobe, M., Russo, G., Haney, J. A., Zmijewski, C., and Croce, C. M.: Human TCRγ/δ + T lymphocytes recognize tetanus toxoid in an MHC-restricted fashion.J Exp Med 169: 1847–1851, 1989
Kuziel, W. A., Takashima, A., Bonyhadi, M., Bergstresser, P. R., Allison, J. P., Tigelaar, R. E., and Tucker, P. W.: Regulation of T-cell receptor y-chain RNA expression in murine Thy-1+ dendritic epidermal cells.Nature 328: 263–266, 1987
Lanier, L., Ruitenberg, J., Bolhuis, R. H., Borst, J., Philips, J. H., and Testi, R.: Structural and serological heterogeneity of the γ/δ T cell antigen receptor expression in thymus and peripheral blood.Eur J Immunol 18: 1985–1992, 1988
LeFranc, M.-P., Forster, A., Baer, R., Stinson, M. A., and Rabbits, T. H.: Diversity and rearrangement of the human T cell rearranging γ genes: nine germ-line variable genes belonging to two subgroups.Cell 45: 237–246, 1986
Lew, A. M., Pardoll, D. M., Maloy, W. L., Fowlkes, B. J., Kruisbeek, A., Cheng, S. F., Germain, R. N., Bluestone, J. A., Schwartz, R. N., and Coligan, J. E.: Characterization of T cell receptor gamma chain expression in a subset of murine thymocytes.Science 234:1401–1405, 1986
Loh, E. Y., Elliott, J. F., Cwirla, S., Lanier, L. L., and Davis, M. M.: Polymerase chain reaction with single-sided specificity: analysis of T cell receptor δ chain.Science 243: 217–220, 1989
Mami-Chouaib, F., Jitsukawa, S., Faure, F., Vasina, B., Genevee, C., Hercend, T., and Triebel, F.: cDNA cloning of functional T cell receptor γ/δ chains expressed in human peripheral blood lymphocytes.Eur J Immunol 19: 1545–1549, 1989
Marrack, P. and Kappler, J.: The antigen-specific major histocompatibility complex restricted receptor on T cells.In F. J. Dixon (ed.):Advances in Immunology, Vol 38, pp. 1–24, Academic, London, 1986
Mingari, M. C., Varese, P., Bottino, C., Melioli, G., Moretta, A., and Moretta, L.: Clonal analysis of CD4−CD8− human thymocytes expressing a T cell receptor γ/δ chain. Direct evidence for the novo expression of CD8 surface antigen and of cytolytic activity against tumor targets.Eur J Immunol 18: 1831–1834, 1988
Moingeon, P., Jitsukawa, S., Faure, F., Troalen, F., Triebel, F., Graziani, M., Forestier, F., Bellet, D., Bohuon, C., and Hercend, T.: A γ-chain complex forms a functional receptor on cloned human lymphocytes with natural killer-like activity.Nature 325: 723–726, 1987
O'Brien, R. L., Happ, M. P., Dallas, A., Palmer, E., Kubo, R., and Born, W. K.: Stimulation of a major subset of lymphocytes expressing T cell receptor γδ by an antigen derived from mycobacterium tuberculosis.Cell 57: 667–674, 1989
Pardoll, D. M., Fowlkes, B. J., Lew, A. M., Maloy, W. L., Weston, M. A., Bluestone, J. A., Schwartz, R. H., Coligan, J. E., and Kruisbeek, A. M.: Thymus dependent and thymus independent developmental pathways for peripheral T cell receptor γδ bearing lymphocytes.J Immunol 140: 4091–4096, 1988
Stingl, G., Koning, F., Yamada, H., Yokoyama, W. M., Tschachler, E., Bluestone, J. A., Steiner, G., Samelson, L. E., Lew, A. M., Coligan, J. E., and Shevach, E. M.: Thy-1− dendritic epidermal cells express T3 antigen and the T-cell receptor γ chain.Proc Natl Acad Sci USA 84 4586–4590, 1987
Takihara, Y., Reimann, J., Michalopoulos, E., Ciccone, E., Moretta, L., and Mak, T. W.: Diversity and structure of human T cell receptor γ chain genes in peripheral blood γ/δ-bearing T lymphocytes.J Exp Med 169: 393–405, 1989
Triebel, F., Faure, F., Graziani, M., Jitsukawa, S., LeFranc, M.-P., and Hercend, T.: A unique V-J-C rearranged gene encodes a y protein expressed on the majority of CD3+ Tcα/β− circulating lymphocytes.J Exp Med 167: 694–699, 1988
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Vietor, H., Koning, F. γδ T-cell receptor repertoire in human peripheral blood and thymus. Immunogenetics 31, 340–346 (1990). https://doi.org/10.1007/BF02115008
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF02115008