Skip to main content
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1989 Nov 1;170(5):1521–1535. doi: 10.1084/jem.170.5.1521

Molecular analysis of human gamma/delta+ clones from thymus and peripheral blood

PMCID: PMC2189499  PMID: 2572670

Abstract

We analyzed the V gamma and V delta gene usage in TCR-gamma/delta- bearing T cell clones isolated from human peripheral blood and postnatal thymus using V-specific mAbs and Southern and Northern analyses. In peripheral blood most of the gamma/delta cells express the V gamma 9-JP-C gamma 1 chain paired with a delta chain bearing the V delta 2 gene product. This heterodimer is very rare in the postnatal thymus, where a different and less restricted pairing of V gamma 9 and V delta 2 chains is found. These findings indicate that physical constraints cannot explain the overrepresentation of a particular V gamma 9-JP/V delta 2 heterodimer in the peripheral blood, and we discuss alternative mechanisms that may account for this differential distribution. In addition, this analysis allowed us to map the specificity of the delta TCS1 mAb to V delta 1-J delta 1 and to identify at least five different expressed V delta genes.

Full Text

The Full Text of this article is available as a PDF (1.2 MB).

Selected References

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

  1. Baer R., Boehm T., Yssel H., Spits H., Rabbitts T. H. Complex rearrangements within the human J delta-C delta/J alpha-C alpha locus and aberrant recombination between J alpha segments. EMBO J. 1988 Jun;7(6):1661–1668. doi: 10.1002/j.1460-2075.1988.tb02993.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. 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]
  3. Boehm T., Baer R., Lavenir I., Forster A., Waters J. J., Nacheva E., Rabbitts T. H. The mechanism of chromosomal translocation t(11;14) involving the T-cell receptor C delta locus on human chromosome 14q11 and a transcribed region of chromosome 11p15. EMBO J. 1988 Feb;7(2):385–394. doi: 10.1002/j.1460-2075.1988.tb02825.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Boehm T., Buluwela L., Williams D., White L., Rabbitts T. H. A cluster of chromosome 11p13 translocations found via distinct D-D and D-D-J rearrangements of the human T cell receptor delta chain gene. EMBO J. 1988 Jul;7(7):2011–2017. doi: 10.1002/j.1460-2075.1988.tb03040.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Brenner M. B., Strominger J. L., Krangel M. S. The gamma delta T cell receptor. Adv Immunol. 1988;43:133–192. [PubMed] [Google Scholar]
  6. Chomczynski P., Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. doi: 10.1006/abio.1987.9999. [DOI] [PubMed] [Google Scholar]
  7. Davis M. M., Bjorkman P. J. T-cell antigen receptor genes and T-cell recognition. Nature. 1988 Aug 4;334(6181):395–402. doi: 10.1038/334395a0. [DOI] [PubMed] [Google Scholar]
  8. Elliott J. F., Rock E. P., Patten P. A., Davis M. M., Chien Y. H. The adult T-cell receptor delta-chain is diverse and distinct from that of fetal thymocytes. Nature. 1988 Feb 18;331(6157):627–631. doi: 10.1038/331627a0. [DOI] [PubMed] [Google Scholar]
  9. 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]
  10. 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]
  11. Forster A., Huck S., Ghanem N., Lefranc M. P., Rabbitts T. H. New subgroups in the human T cell rearranging V gamma gene locus. EMBO J. 1987 Jul;6(7):1945–1950. doi: 10.1002/j.1460-2075.1987.tb02456.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. 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]
  13. Hata S., Clabby M., Devlin P., Spits H., De Vries J. E., Krangel M. S. Diversity and organization of human T cell receptor delta variable gene segments. J Exp Med. 1989 Jan 1;169(1):41–57. doi: 10.1084/jem.169.1.41. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Hata S., Satyanarayana K., Devlin P., Band H., McLean J., Strominger J. L., Brenner M. B., Krangel M. S. Extensive junctional diversity of rearranged human T cell receptor delta genes. Science. 1988 Jun 10;240(4858):1541–1544. doi: 10.1126/science.3259726. [DOI] [PubMed] [Google Scholar]
  15. Havran W. L., Allison J. P. Developmentally ordered appearance of thymocytes expressing different T-cell antigen receptors. Nature. 1988 Sep 29;335(6189):443–445. doi: 10.1038/335443a0. [DOI] [PubMed] [Google Scholar]
  16. Lanier L. L., Ruitenberg J., Bolhuis R. L., Borst J., Phillips J. H., Testi R. Structural and serological heterogeneity of gamma/delta T cell antigen receptor expression in thymus and peripheral blood. Eur J Immunol. 1988 Dec;18(12):1985–1992. doi: 10.1002/eji.1830181218. [DOI] [PubMed] [Google Scholar]
  17. Lanzavecchia A. Antigen-specific interaction between T and B cells. Nature. 1985 Apr 11;314(6011):537–539. doi: 10.1038/314537a0. [DOI] [PubMed] [Google Scholar]
  18. Lefranc M. P., Forster A., Rabbitts T. H. Genetic polymorphism and exon changes of the constant regions of the human T-cell rearranging gene gamma. Proc Natl Acad Sci U S A. 1986 Dec;83(24):9596–9600. doi: 10.1073/pnas.83.24.9596. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. 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]
  20. Loh E. Y., Cwirla S., Serafini A. T., Phillips J. H., Lanier L. L. Human T-cell-receptor delta chain: genomic organization, diversity, and expression in populations of cells. Proc Natl Acad Sci U S A. 1988 Dec;85(24):9714–9718. doi: 10.1073/pnas.85.24.9714. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Loh E. Y., Elliott J. F., Cwirla S., Lanier L. L., Davis M. M. Polymerase chain reaction with single-sided specificity: analysis of T cell receptor delta chain. Science. 1989 Jan 13;243(4888):217–220. doi: 10.1126/science.2463672. [DOI] [PubMed] [Google Scholar]
  22. Maniatis T., Hardison R. C., Lacy E., Lauer J., O'Connell C., Quon D., Sim G. K., Efstratiadis A. The isolation of structural genes from libraries of eucaryotic DNA. Cell. 1978 Oct;15(2):687–701. doi: 10.1016/0092-8674(78)90036-3. [DOI] [PubMed] [Google Scholar]
  23. 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]
  24. 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]
  25. 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]
  26. 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]
  27. 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]
  28. 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]
  29. 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]
  30. Toyonaga B., Mak T. W. Genes of the T-cell antigen receptor in normal and malignant T cells. Annu Rev Immunol. 1987;5:585–620. doi: 10.1146/annurev.iy.05.040187.003101. [DOI] [PubMed] [Google Scholar]
  31. Tribel F., Lefranc M. P., Hercend T. Further evidence for a sequentially ordered activation of T cell rearranging gamma genes during T lymphocyte differentiation. Eur J Immunol. 1988 May;18(5):789–794. doi: 10.1002/eji.1830180520. [DOI] [PubMed] [Google Scholar]
  32. 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]
  33. 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]
  34. Wu Y. J., Tian W. T., Snider R. M., Rittershaus C., Rogers P., LaManna L., Ip S. H. Signal transduction of gamma/delta T cell antigen receptor with a novel mitogenic anti-delta antibody. J Immunol. 1988 Sep 1;141(5):1476–1479. [PubMed] [Google Scholar]
  35. de Villartay J. P., Hockett R. D., Coran D., Korsmeyer S. J., Cohen D. I. Deletion of the human T-cell receptor delta-gene by a site-specific recombination. Nature. 1988 Sep 8;335(6186):170–174. doi: 10.1038/335170a0. [DOI] [PubMed] [Google Scholar]

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

RESOURCES