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The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1993 Jan;91(1):171–178. doi: 10.1172/JCI116167

Regulation of the mature human T cell receptor gamma repertoire by biased V-J gene rearrangement.

H Kohsaka 1, P P Chen 1, A Taniguchi 1, W E Ollier 1, D A Carson 1
PMCID: PMC330011  PMID: 7678601

Abstract

To delineate how gene rearrangement influences the expressed human gamma delta T cell repertoire, we generated T cell receptor gamma (TCR gamma) V domain-specific cDNA libraries from the peripheral lymphocytes of eight donors and sequenced a total of 232 TCR gamma gene transcripts. The libraries consisted of both in-frame and out-of-frame rearranged TCR gamma genes. The in-frame TCR gamma gene transcripts were used to determine the diversity of functional T cells, whereas the out-of-frame transcripts, primarily derived from alpha beta T cells, were used to assess the frequencies of TCR V gamma-J gamma rearrangements in progenitor T lymphocytes. The results showed that both sets of transcripts exhibited strikingly restricted V gamma-J gamma combinations. Only 11 of 40 potential V gamma-J gamma rearrangements were common ( > or = 3% of total). The pattern of gene usage in the functional and nonfunctional transcripts was similar and did not differ markedly among donors. The only exception was the predominance of V gamma 9-JP in potentially functional transcripts from seven of eight individuals. These results show that V gamma-J gamma rearrangement is nonrandom and suggest that the diversity of TCR gamma genes in the functional gamma delta T cell repertoire partly depends upon preferentially rearranged V gamma-J gamma gene combinations. However, the expansion of V gamma 9/V gamma 2 T cells in adult peripheral blood can only be explained by antigenic selection of relatively rare V gamma 9-JP recombinants.

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Selected References

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

  1. Allison J. P., Havran W. L. The immunobiology of T cells with invariant gamma delta antigen receptors. Annu Rev Immunol. 1991;9:679–705. doi: 10.1146/annurev.iy.09.040191.003335. [DOI] [PubMed] [Google Scholar]
  2. Bill J., Kanagawa O., Woodland D. L., Palmer E. The MHC molecule I-E is necessary but not sufficient for the clonal deletion of V beta 11-bearing T cells. J Exp Med. 1989 Apr 1;169(4):1405–1419. doi: 10.1084/jem.169.4.1405. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Brenner M. B., Strominger J. L., Krangel M. S. The gamma delta T cell receptor. Adv Immunol. 1988;43:133–192. [PubMed] [Google Scholar]
  4. 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]
  5. De Libero G., Casorati G., Giachino C., Carbonara C., Migone N., Matzinger P., Lanzavecchia A. Selection by two powerful antigens may account for the presence of the major population of human peripheral gamma/delta T cells. J Exp Med. 1991 Jun 1;173(6):1311–1322. doi: 10.1084/jem.173.6.1311. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Doherty P. J., Yang S. X., Laxer R. M., Silverman E. D., Inman R., Pan S. Evidence for clonal expansion of T cell receptor V gamma II+ T cells in the synovial fluid of patients with arthritis. J Immunol. 1992 Jul 1;149(1):295–299. [PubMed] [Google Scholar]
  7. 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]
  8. Fagioli M., Ciccone E., Bottino C., Falini B., Grignani F., Moretta A., Moretta L., Pelicci P. G. The C gamma 1-encoded disulphide-linked and the C gamma 2-encoded nondisulphide-linked forms of the gamma/delta heterodimer use different gamma and delta variable regions. Blood. 1990 Jul 15;76(2):279–284. [PubMed] [Google Scholar]
  9. Falini B., Flenghi L., Pileri S., Pelicci P., Fagioli M., Martelli M. F., Moretta L., Ciccone E. Distribution of T cells bearing different forms of the T cell receptor gamma/delta in normal and pathological human tissues. J Immunol. 1989 Oct 15;143(8):2480–2488. [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. Feeney A. J. Junctional sequences of fetal T cell receptor beta chains have few N regions. J Exp Med. 1991 Jul 1;174(1):115–124. doi: 10.1084/jem.174.1.115. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Feeney A. J. Lack of N regions in fetal and neonatal mouse immunoglobulin V-D-J junctional sequences. J Exp Med. 1990 Nov 1;172(5):1377–1390. doi: 10.1084/jem.172.5.1377. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Fisch P., Malkovsky M., Kovats S., Sturm E., Braakman E., Klein B. S., Voss S. D., Morrissey L. W., DeMars R., Welch W. J. Recognition by human V gamma 9/V delta 2 T cells of a GroEL homolog on Daudi Burkitt's lymphoma cells. Science. 1990 Nov 30;250(4985):1269–1273. doi: 10.1126/science.1978758. [DOI] [PubMed] [Google Scholar]
  14. 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]
  15. George J. F., Jr, Schroeder H. W., Jr Developmental regulation of D beta reading frame and junctional diversity in T cell receptor-beta transcripts from human thymus. J Immunol. 1992 Feb 15;148(4):1230–1239. [PubMed] [Google Scholar]
  16. Ishida I., Verbeek S., Bonneville M., Itohara S., Berns A., Tonegawa S. T-cell receptor gamma delta and gamma transgenic mice suggest a role of a gamma gene silencer in the generation of alpha beta T cells. Proc Natl Acad Sci U S A. 1990 Apr;87(8):3067–3071. doi: 10.1073/pnas.87.8.3067. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Kappler J. W., Roehm N., Marrack P. T cell tolerance by clonal elimination in the thymus. Cell. 1987 Apr 24;49(2):273–280. doi: 10.1016/0092-8674(87)90568-x. [DOI] [PubMed] [Google Scholar]
  18. Kimura N., Du R. P., Mak T. W. Rearrangement and organization of T cell receptor gamma chain genes in human leukemic T cell lines. Eur J Immunol. 1987 Nov;17(11):1653–1656. doi: 10.1002/eji.1830171121. [DOI] [PubMed] [Google Scholar]
  19. Krangel M. S., Yssel H., Brocklehurst C., Spits H. A distinct wave of human T cell receptor gamma/delta lymphocytes in the early fetal thymus: evidence for controlled gene rearrangement and cytokine production. J Exp Med. 1990 Sep 1;172(3):847–859. doi: 10.1084/jem.172.3.847. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. 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]
  21. Liao N. S., Maltzman J., Raulet D. H. Positive selection determines T cell receptor V beta 14 gene usage by CD8+ T cells. J Exp Med. 1989 Jul 1;170(1):135–143. doi: 10.1084/jem.170.1.135. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. 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]
  23. McVay L. D., Carding S. R., Bottomly K., Hayday A. C. Regulated expression and structure of T cell receptor gamma/delta transcripts in human thymic ontogeny. EMBO J. 1991 Jan;10(1):83–91. doi: 10.1002/j.1460-2075.1991.tb07923.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Olive C., Gatenby P. A., Serjeantson S. W. Variable gene usage of T cell receptor gamma- and delta-chain transcripts expressed in synovia and peripheral blood of patients with rheumatoid arthritis. Clin Exp Immunol. 1992 Feb;87(2):172–177. doi: 10.1111/j.1365-2249.1992.tb02970.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Parker C. M., Groh V., Band H., Porcelli S. A., Morita C., Fabbi M., Glass D., Strominger J. L., Brenner M. B. Evidence for extrathymic changes in the T cell receptor gamma/delta repertoire. J Exp Med. 1990 May 1;171(5):1597–1612. doi: 10.1084/jem.171.5.1597. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. 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]
  27. Rust C. J., Verreck F., Vietor H., Koning F. Specific recognition of staphylococcal enterotoxin A by human T cells bearing receptors with the V gamma 9 region. Nature. 1990 Aug 9;346(6284):572–574. doi: 10.1038/346572a0. [DOI] [PubMed] [Google Scholar]
  28. Sanger F. Determination of nucleotide sequences in DNA. Science. 1981 Dec 11;214(4526):1205–1210. doi: 10.1126/science.7302589. [DOI] [PubMed] [Google Scholar]
  29. Sha W. C., Nelson C. A., Newberry R. D., Kranz D. M., Russell J. H., Loh D. Y. Positive and negative selection of an antigen receptor on T cells in transgenic mice. Nature. 1988 Nov 3;336(6194):73–76. doi: 10.1038/336073a0. [DOI] [PubMed] [Google Scholar]
  30. Sturm E., Braakman E., Fisch P., Vreugdenhil R. J., Sondel P., Bolhuis R. L. Human V gamma 9-V delta 2 T cell receptor-gamma delta lymphocytes show specificity to Daudi Burkitt's lymphoma cells. J Immunol. 1990 Nov 15;145(10):3202–3208. [PubMed] [Google Scholar]
  31. Takeshita S., Toda M., Yamagishi H. Excision products of the T cell receptor gene support a progressive rearrangement model of the alpha/delta locus. EMBO J. 1989 Nov;8(11):3261–3270. doi: 10.1002/j.1460-2075.1989.tb08486.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. 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]
  33. 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]
  34. Yoshikai Y., Toyonaga B., Koga Y., Kimura N., Griesser H., Mak T. W. Repertoire of the human T cell gamma genes: high frequency of nonfunctional transcripts in thymus and mature T cells. Eur J Immunol. 1987 Jan;17(1):119–126. doi: 10.1002/eji.1830170120. [DOI] [PubMed] [Google Scholar]

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