Skip to main content
NCBI home page
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1988 Aug 1;168(2):491–505. doi: 10.1084/jem.168.2.491

Two subsets of human T lymphocytes expressing gamma/delta antigen receptor are identifiable by monoclonal antibodies directed to two distinct molecular forms of the receptor

PMCID: PMC2189015  PMID: 2970517

Abstract

Two mAbs directed to the TCR-gamma/delta were analyzed for their pattern of reactivity with CD3+WT31- cell populations or clones. In normal individuals, the BB3 mAb reacted with approximately 2/3 of peripheral blood CD3+WT31- lymphocytes, whereas delta-TCS-1 stained approximately 1/3 of such cells. In addition, the sum of the percentages of BB3+ and delta-TCS-1+ cells approximated the percentages of peripheral blood CD3+WT31- lymphocytes in seven normal donors tested. Also, in peripheral blood-derived polyclonal CD3+WT31- populations, cultured in IL-2, cells reacting with one or another mAb accounted for the whole cell population. On the other hand, only delta- TCS-1-reactive cells, but not BB3+ cells, could be detected in unfractionated as well as in CD4-8-thymocyte populations. Analysis of peripheral blood-derived CD3+WT31- clones showed that 70% of 72 clones analyzed reacted with BB3 mAb, but not with delta-TCS-1 mAb. On the other hand, delta-TCS-1 mAb stained the remaining BB3- clones. Five clones expressing medium-low amounts of CD8 antigen were BB3- delta-TCS- 1+. Both types of clones lysed the Fc gamma receptor-bearing P815 target cell in the presence of anti-CD3 mAb (but not of mAb directed against HLA-DR, CD7 molecules, or TCR-alpha/beta). In this cytolytic assay, BB3 mAb induced target cell lysis only by BB3+ clones, whereas delta-TCS-1 mAb was effective only with delta-TCS-1+ clones. The CD3- associated surface molecules expressed by BB3+ or delta-TCS-1+ clones were analyzed after cell surface iodination and immunoprecipitation with the corresponding anti-TCR mAb or with anti-CD3 mAb (in digitonin- containing buffer). In SDS-PAGE, molecules immunoprecipitated from 13 BB3+ clones displayed, under nonreducing conditions, a molecular weight of 80 kD (in some cases, a minor 38-kD band could be detected). Under reducing conditions, two major components of 44 and 41 kD (and a minor component of 38 kD) were detected. On the other hand, TCR molecules immunoprecipitated from 11 different delta-TCS-1+ clones appeared as a diffuse band of 41-44 kD, both under reducing and nonreducing conditions (under non-reducing condition, an additional 38-kD band was present). Therefore, BB3+ cells express a disulphide-linked form of TCR- gamma/delta whereas delta-TCS-1+ cells express a non-disulphide-linked form.(ABSTRACT TRUNCATED AT 400 WORDS)

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. 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]
  2. 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]
  3. Brenner M. B., McLean J., Dialynas D. P., Strominger J. L., Smith J. A., Owen F. L., Seidman J. G., Ip S., Rosen F., Krangel M. S. Identification of a putative second T-cell receptor. Nature. 1986 Jul 10;322(6075):145–149. doi: 10.1038/322145a0. [DOI] [PubMed] [Google Scholar]
  4. Brenner M. B., Trowbridge I. S., Strominger J. L. Cross-linking of human T cell receptor proteins: association between the T cell idiotype beta subunit and the T3 glycoprotein heavy subunit. Cell. 1985 Jan;40(1):183–190. doi: 10.1016/0092-8674(85)90321-6. [DOI] [PubMed] [Google Scholar]
  5. Chien Y. H., Iwashima M., Kaplan K. B., Elliott J. F., Davis M. M. A new T-cell receptor gene located within the alpha locus and expressed early in T-cell differentiation. 1987 Jun 25-Jul 1Nature. 327(6124):677–682. doi: 10.1038/327677a0. [DOI] [PubMed] [Google Scholar]
  6. Ciccone E., Ferrini S., Bottino C., Viale O., Prigione I., Pantaleo G., Tambussi G., Moretta A., Moretta L. A monoclonal antibody specific for a common determinant of the human T cell receptor gamma/delta directly activates CD3+WT31- lymphocytes to express their functional program(s). J Exp Med. 1988 Jul 1;168(1):1–11. doi: 10.1084/jem.168.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. 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]
  8. Ferrini S., Bottino C., Biassoni R., Poggi A., Sekaly R. P., Moretta L., Moretta A. Characterization of CD3+, CD4-, CD8- clones expressing the putative T cell receptor gamma gene product. Analysis of the activation pathways leading to interleukin 2 production and triggering of the lytic machinery. J Exp Med. 1987 Jul 1;166(1):277–282. doi: 10.1084/jem.166.1.277. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Fleischer B. Lysis of bystander target cells after triggering of human cytotoxic T lymphocytes. Eur J Immunol. 1986 Aug;16(8):1021–1024. doi: 10.1002/eji.1830160826. [DOI] [PubMed] [Google Scholar]
  10. Hata S., Brenner M. B., Krangel M. S. Identification of putative human T cell receptor delta complementary DNA clones. Science. 1987 Oct 30;238(4827):678–682. doi: 10.1126/science.3499667. [DOI] [PubMed] [Google Scholar]
  11. Hayday A. C., Saito H., Gillies S. D., Kranz D. M., Tanigawa G., Eisen H. N., Tonegawa S. Structure, organization, and somatic rearrangement of T cell gamma genes. Cell. 1985 Feb;40(2):259–269. doi: 10.1016/0092-8674(85)90140-0. [DOI] [PubMed] [Google Scholar]
  12. Hoffman R. W., Bluestone J. A., Leo O., Shaw S. Lysis of anti-T3-bearing murine hybridoma cells by human allospecific cytotoxic T cell clones and inhibition of that lysis by anti-T3 and anti-LFA-1 antibodies. J Immunol. 1985 Jul;135(1):5–8. [PubMed] [Google Scholar]
  13. Hubbard A. L., Cohn Z. A. Externally disposed plasma membrane proteins. I. Enzymatic iodination of mouse L cells. J Cell Biol. 1975 Feb;64(2):438–460. doi: 10.1083/jcb.64.2.438. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. 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]
  15. 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]
  16. Kranz D. M., Saito H., Heller M., Takagaki Y., Haas W., Eisen H. N., Tonegawa S. Limited diversity of the rearranged T-cell gamma gene. 1985 Feb 28-Mar 6Nature. 313(6005):752–755. doi: 10.1038/313752a0. [DOI] [PubMed] [Google Scholar]
  17. Lanier L. L., Federspiel N. A., Ruitenberg J. J., Phillips J. H., Allison J. P., Littman D., Weiss A. The T cell antigen receptor complex expressed on normal peripheral blood CD4-, CD8- T lymphocytes. A CD3-associated disulfide-linked gamma chain heterodimer. J Exp Med. 1987 Apr 1;165(4):1076–1094. doi: 10.1084/jem.165.4.1076. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Lanier L. L., Weiss A. Presence of Ti (WT31) negative T lymphocytes in normal blood and thymus. Nature. 1986 Nov 20;324(6094):268–270. doi: 10.1038/324268a0. [DOI] [PubMed] [Google Scholar]
  19. Lefranc M. P., Forster A., Rabbitts T. H. Rearrangement of two distinct T-cell gamma-chain variable-region genes in human DNA. 1986 Jan 30-Feb 5Nature. 319(6052):420–422. doi: 10.1038/319420a0. [DOI] [PubMed] [Google Scholar]
  20. Lefranc M. P., Rabbitts T. H. Two tandemly organized human genes encoding the T-cell gamma constant-region sequences show multiple rearrangement in different T-cell types. Nature. 1985 Aug 1;316(6027):464–466. doi: 10.1038/316464a0. [DOI] [PubMed] [Google Scholar]
  21. Loh E. Y., Lanier L. L., Turck C. W., Littman D. R., Davis M. M., Chien Y. H., Weiss A. Identification and sequence of a fourth human T cell antigen receptor chain. Nature. 1987 Dec 10;330(6148):569–572. doi: 10.1038/330569a0. [DOI] [PubMed] [Google Scholar]
  22. 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]
  23. 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]
  24. Moretta A., Olive D., Poggi A., Pantaleo G., Mawas C., Moretta L. Modulation of surface T11 molecules induced by monoclonal antibodies: analysis of the functional relationship between antigen-dependent and antigen-independent pathways of human T cell activation. Eur J Immunol. 1986 Nov;16(11):1427–1432. doi: 10.1002/eji.1830161118. [DOI] [PubMed] [Google Scholar]
  25. Moretta A., Pantaleo G., Moretta L., Cerottini J. C., Mingari M. C. Direct demonstration of the clonogenic potential of every human peripheral blood T cell. Clonal analysis of HLA-DR expression and cytolytic activity. J Exp Med. 1983 Feb 1;157(2):743–754. doi: 10.1084/jem.157.2.743. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Moretta A., Poggi A., Olive D., Bottino C., Fortis C., Pantaleo G., Moretta L. Selection and characterization of T-cell variants lacking molecules involved in T-cell activation (T3 T-cell receptor, T44, and T11): analysis of the functional relationship among different pathways of activation. Proc Natl Acad Sci U S A. 1987 Mar;84(6):1654–1658. doi: 10.1073/pnas.84.6.1654. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Moretta L., Pende D., Bottino C., Migone N., Ciccone E., Ferrini S., Mingari M. C., Moretta A. Human CD3+4-8-WT31- T lymphocyte populations expressing the putative T cell receptor gamma-gene product. A limiting dilution and clonal analysis. Eur J Immunol. 1987 Sep;17(9):1229–1234. doi: 10.1002/eji.1830170903. [DOI] [PubMed] [Google Scholar]
  28. Pantaleo G., Ferrini S., Zocchi M. R., Bottino C., Biassoni R., Moretta L., Moretta A. Analysis of signal transducing mechanisms in CD3+ CD4- CD8- cells expressing the putative T cell receptor gamma gene product. J Immunol. 1987 Dec 1;139(11):3580–3584. [PubMed] [Google Scholar]
  29. Pelicci P. G., Subar M., Weiss A., Dalla-Favera R., Littman D. R. Molecular diversity of the human T-gamma constant region genes. Science. 1987 Aug 28;237(4818):1051–1055. doi: 10.1126/science.3112943. [DOI] [PubMed] [Google Scholar]
  30. Poggi A., Bottino C., Zocchi M. R., Pantaleo G., Ciccone E., Mingari C., Moretta L., Moretta A. CD3+ WT31- peripheral T lymphocytes lack T44 (CD28), a surface molecule involved in activation of T cells bearing the alpha/beta heterodimer. Eur J Immunol. 1987 Jul;17(7):1065–1068. doi: 10.1002/eji.1830170725. [DOI] [PubMed] [Google Scholar]
  31. Quertermous T., Murre C., Dialynas D., Duby A. D., Strominger J. L., Waldman T. A., Seidman J. G. Human T-cell gamma chain genes: organization, diversity, and rearrangement. Science. 1986 Jan 17;231(4735):252–255. doi: 10.1126/science.3079918. [DOI] [PubMed] [Google Scholar]
  32. Reinherz E. L., Meuer S. C., Fitzgerald K. A., Hussey R. E., Hodgdon J. C., Acuto O., Schlossman S. F. Comparison of T3-associated 49- and 43-kilodalton cell surface molecules on individual human T-cell clones: evidence for peptide variability in T-cell receptor structures. Proc Natl Acad Sci U S A. 1983 Jul;80(13):4104–4108. doi: 10.1073/pnas.80.13.4104. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Saito H., Kranz D. M., Takagaki Y., Hayday A. C., Eisen H. N., Tonegawa S. Complete primary structure of a heterodimeric T-cell receptor deduced from cDNA sequences. 1984 Jun 28-Jul 4Nature. 309(5971):757–762. doi: 10.1038/309757a0. [DOI] [PubMed] [Google Scholar]
  34. Spits H., Borst J., Tax W., Capel P. J., Terhorst C., de Vries J. E. Characteristics of a monoclonal antibody (WT-31) that recognizes a common epitope on the human T cell receptor for antigen. J Immunol. 1985 Sep;135(3):1922–1928. [PubMed] [Google Scholar]
  35. Weiss A., Newton M., Crommie D. Expression of T3 in association with a molecule distinct from the T-cell antigen receptor heterodimer. Proc Natl Acad Sci U S A. 1986 Sep;83(18):6998–7002. doi: 10.1073/pnas.83.18.6998. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Weiss A., Stobo J. D. Requirement for the coexpression of T3 and the T cell antigen receptor on a malignant human T cell line. J Exp Med. 1984 Nov 1;160(5):1284–1299. doi: 10.1084/jem.160.5.1284. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES