Skip to main content
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1996 Oct 1;93(20):11025–11028. doi: 10.1073/pnas.93.20.11025

Essential requirement of an invariant V alpha 14 T cell antigen receptor expression in the development of natural killer T cells.

M Taniguchi 1, H Koseki 1, T Tokuhisa 1, K Masuda 1, H Sato 1, E Kondo 1, T Kawano 1, J Cui 1, A Perkes 1, S Koyasu 1, Y Makino 1
PMCID: PMC38277  PMID: 8855302

Abstract

NK1.1+ T [natural killer (NK) T] cells express an invariant T cell antigen receptor alpha chain (TCR alpha) encoded by V alpha 14 and J alpha 281 segments in association with a limited number of V betas, predominantly V beta 8.2. Expression of the invariant V alpha 14/J alpha 281, but not V alpha 1, TCR in transgenic mice lacking endogenous TCR alpha expression blocks the development of conventional T alpha beta cells and leads to the preferential development of V alpha 14 NK T cells, suggesting a prerequisite role of invariant V alpha 14 TCR in NK T cell development. In V beta 8.2 but not B beta 3 transgenic mice, two NK T cells with different CD3 epsilon expressions, CD3 epsilon(dim) and CD3 epsilon(high), can be identified. CD3 epsilon(high) NK T cells express surface V alpha 14/V beta 8 TCR, indicating a mature cell type, whereas CD3 epsilon(dim) NK T cells express V beta 8 without V alpha 14 TCR and no significant CD3 epsilon expression (CD3 epsilon(dim)) on the cell surface. However, the latter are positive for recombination activating gene (RAG-1 and RAG-2) mRNA, which are only expressed in the precursor or immature T cell lineage, and also possess CD3 epsilon mRNA in their cytoplasm, suggesting that CD3 epsilon(dim) NK T cells are the precursor of V alpha 14 NK T cells.

Full text

PDF
11025

Images in this article

Selected References

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

  1. Adachi Y., Koseki H., Zijlstra M., Taniguchi M. Positive selection of invariant V alpha 14+ T cells by non-major histocompatibility complex-encoded class I-like molecules expressed on bone marrow-derived cells. Proc Natl Acad Sci U S A. 1995 Feb 14;92(4):1200–1204. doi: 10.1073/pnas.92.4.1200. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Ballas Z. K., Rasmussen W. NK1.1+ thymocytes. Adult murine CD4-, CD8- thymocytes contain an NK1.1+, CD3+, CD5hi, CD44hi, TCR-V beta 8+ subset. J Immunol. 1990 Aug 15;145(4):1039–1045. [PubMed] [Google Scholar]
  3. Bendelac A., Killeen N., Littman D. R., Schwartz R. H. A subset of CD4+ thymocytes selected by MHC class I molecules. Science. 1994 Mar 25;263(5154):1774–1778. doi: 10.1126/science.7907820. [DOI] [PubMed] [Google Scholar]
  4. Bendelac A., Lantz O., Quimby M. E., Yewdell J. W., Bennink J. R., Brutkiewicz R. R. CD1 recognition by mouse NK1+ T lymphocytes. Science. 1995 May 12;268(5212):863–865. doi: 10.1126/science.7538697. [DOI] [PubMed] [Google Scholar]
  5. Berg L. J., Fazekas de St Groth B., Pullen A. M., Davis M. M. Phenotypic differences between alpha beta versus beta T-cell receptor transgenic mice undergoing negative selection. Nature. 1989 Aug 17;340(6234):559–562. doi: 10.1038/340559a0. [DOI] [PubMed] [Google Scholar]
  6. Bix M., Coles M., Raulet D. Positive selection of V beta 8+ CD4-8- thymocytes by class I molecules expressed by hematopoietic cells. J Exp Med. 1993 Sep 1;178(3):901–908. doi: 10.1084/jem.178.3.901. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Coles M. C., Raulet D. H. Class I dependence of the development of CD4+ CD8- NK1.1+ thymocytes. J Exp Med. 1994 Jul 1;180(1):395–399. doi: 10.1084/jem.180.1.395. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Fowlkes B. J., Kruisbeek A. M., Ton-That H., Weston M. A., Coligan J. E., Schwartz R. H., Pardoll D. M. A novel population of T-cell receptor alpha beta-bearing thymocytes which predominantly expresses a single V beta gene family. Nature. 1987 Sep 17;329(6136):251–254. doi: 10.1038/329251a0. [DOI] [PubMed] [Google Scholar]
  9. Grawunder U., Leu T. M., Schatz D. G., Werner A., Rolink A. G., Melchers F., Winkler T. H. Down-regulation of RAG1 and RAG2 gene expression in preB cells after functional immunoglobulin heavy chain rearrangement. Immunity. 1995 Nov;3(5):601–608. doi: 10.1016/1074-7613(95)90131-0. [DOI] [PubMed] [Google Scholar]
  10. Hashimoto W., Takeda K., Anzai R., Ogasawara K., Sakihara H., Sugiura K., Seki S., Kumagai K. Cytotoxic NK1.1 Ag+ alpha beta T cells with intermediate TCR induced in the liver of mice by IL-12. J Immunol. 1995 May 1;154(9):4333–4340. [PubMed] [Google Scholar]
  11. Imai K., Kanno M., Kimoto H., Shigemoto K., Yamamoto S., Taniguchi M. Sequence and expression of transcripts of the T-cell antigen receptor alpha-chain gene in a functional, antigen-specific suppressor-T-cell hybridoma. Proc Natl Acad Sci U S A. 1986 Nov;83(22):8708–8712. doi: 10.1073/pnas.83.22.8708. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Ito T., Ishibashi K., Imai K., Koseki H., Ra C. S., Fernandez E., Kantake M., Saito T., Taniguchi M. Monoclonal antibody against murine T cell receptor V alpha 14 cross-reacts with human CD3 epsilon and detects disulfide-linked dimeric form. Int Immunol. 1991 Oct;3(10):991–995. doi: 10.1093/intimm/3.10.991. [DOI] [PubMed] [Google Scholar]
  13. Kikly K., Dennert G. Evidence for extrathymic development of TNK cells. NK1+ CD3+ cells responsible for acute marrow graft rejection are present in thymus-deficient mice. J Immunol. 1992 Jul 15;149(2):403–412. [PubMed] [Google Scholar]
  14. Koseki H., Imai K., Nakayama F., Sado T., Moriwaki K., Taniguchi M. Homogenous junctional sequence of the V14+ T-cell antigen receptor alpha chain expanded in unprimed mice. Proc Natl Acad Sci U S A. 1990 Jul;87(14):5248–5252. doi: 10.1073/pnas.87.14.5248. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Koyasu S. CD3+CD16+NK1.1+B220+ large granular lymphocytes arise from both alpha-beta TCR+CD4-CD8- and gamma-delta TCR+CD4-CD8- cells. J Exp Med. 1994 Jun 1;179(6):1957–1972. doi: 10.1084/jem.179.6.1957. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Koyasu S., D'Adamio L., Arulanandam A. R., Abraham S., Clayton L. K., Reinherz E. L. T cell receptor complexes containing Fc epsilon RI gamma homodimers in lieu of CD3 zeta and CD3 eta components: a novel isoform expressed on large granular lymphocytes. J Exp Med. 1992 Jan 1;175(1):203–209. doi: 10.1084/jem.175.1.203. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Lantz O., Bendelac A. An invariant T cell receptor alpha chain is used by a unique subset of major histocompatibility complex class I-specific CD4+ and CD4-8- T cells in mice and humans. J Exp Med. 1994 Sep 1;180(3):1097–1106. doi: 10.1084/jem.180.3.1097. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Levitsky H. I., Golumbek P. T., Pardoll D. M. The fate of CD4-8- T cell receptor-alpha beta+ thymocytes. J Immunol. 1991 Feb 15;146(4):1113–1117. [PubMed] [Google Scholar]
  19. Makino Y., Kanno R., Ito T., Higashino K., Taniguchi M. Predominant expression of invariant V alpha 14+ TCR alpha chain in NK1.1+ T cell populations. Int Immunol. 1995 Jul;7(7):1157–1161. doi: 10.1093/intimm/7.7.1157. [DOI] [PubMed] [Google Scholar]
  20. Makino Y., Kanno R., Koseki H., Taniguchi M. Development of Valpha4+ NK T cells in the early stages of embryogenesis. Proc Natl Acad Sci U S A. 1996 Jun 25;93(13):6516–6520. doi: 10.1073/pnas.93.13.6516. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Makino Y., Yamagata N., Sasho T., Adachi Y., Kanno R., Koseki H., Kanno M., Taniguchi M. Extrathymic development of V alpha 14-positive T cells. J Exp Med. 1993 May 1;177(5):1399–1408. doi: 10.1084/jem.177.5.1399. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Matsuzaki Y., Gyotoku J., Ogawa M., Nishikawa S., Katsura Y., Gachelin G., Nakauchi H. Characterization of c-kit positive intrathymic stem cells that are restricted to lymphoid differentiation. J Exp Med. 1993 Oct 1;178(4):1283–1292. doi: 10.1084/jem.178.4.1283. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Mombaerts P., Clarke A. R., Rudnicki M. A., Iacomini J., Itohara S., Lafaille J. J., Wang L., Ichikawa Y., Jaenisch R., Hooper M. L. Mutations in T-cell antigen receptor genes alpha and beta block thymocyte development at different stages. Nature. 1992 Nov 19;360(6401):225–231. doi: 10.1038/360225a0. [DOI] [PubMed] [Google Scholar]
  24. Moretta L., Ciccone E., Mingari M. C., Biassoni R., Moretta A. Human natural killer cells: origin, clonality, specificity, and receptors. Adv Immunol. 1994;55:341–380. doi: 10.1016/s0065-2776(08)60513-1. [DOI] [PubMed] [Google Scholar]
  25. Ohteki T., MacDonald H. R. Major histocompatibility complex class I related molecules control the development of CD4+8- and CD4-8- subsets of natural killer 1.1+ T cell receptor-alpha/beta+ cells in the liver of mice. J Exp Med. 1994 Aug 1;180(2):699–704. doi: 10.1084/jem.180.2.699. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Rodewald H. R., Moingeon P., Lucich J. L., Dosiou C., Lopez P., Reinherz E. L. A population of early fetal thymocytes expressing Fc gamma RII/III contains precursors of T lymphocytes and natural killer cells. Cell. 1992 Apr 3;69(1):139–150. doi: 10.1016/0092-8674(92)90125-v. [DOI] [PubMed] [Google Scholar]
  27. Shinkai Y., Koyasu S., Nakayama K., Murphy K. M., Loh D. Y., Reinherz E. L., Alt F. W. Restoration of T cell development in RAG-2-deficient mice by functional TCR transgenes. Science. 1993 Feb 5;259(5096):822–825. doi: 10.1126/science.8430336. [DOI] [PubMed] [Google Scholar]
  28. Sumida T., Sakamoto A., Murata H., Makino Y., Takahashi H., Yoshida S., Nishioka K., Iwamoto I., Taniguchi M. Selective reduction of T cells bearing invariant V alpha 24J alpha Q antigen receptor in patients with systemic sclerosis. J Exp Med. 1995 Oct 1;182(4):1163–1168. doi: 10.1084/jem.182.4.1163. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Sykes M. Unusual T cell populations in adult murine bone marrow. Prevalence of CD3+CD4-CD8- and alpha beta TCR+NK1.1+ cells. J Immunol. 1990 Nov 15;145(10):3209–3215. [PubMed] [Google Scholar]
  30. Sánchez M. J., Muench M. O., Roncarolo M. G., Lanier L. L., Phillips J. H. Identification of a common T/natural killer cell progenitor in human fetal thymus. J Exp Med. 1994 Aug 1;180(2):569–576. doi: 10.1084/jem.180.2.569. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Takahama Y., Kosugi A., Singer A. Phenotype, ontogeny, and repertoire of CD4-CD8- T cell receptor alpha beta + thymocytes. Variable influence of self-antigens on T cell receptor V beta usage. J Immunol. 1991 Feb 15;146(4):1134–1141. [PubMed] [Google Scholar]
  32. Takeda K., Dennert G. The development of autoimmunity in C57BL/6 lpr mice correlates with the disappearance of natural killer type 1-positive cells: evidence for their suppressive action on bone marrow stem cell proliferation, B cell immunoglobulin secretion, and autoimmune symptoms. J Exp Med. 1993 Jan 1;177(1):155–164. doi: 10.1084/jem.177.1.155. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Takeda K., Moore M. W., Dennert G. Acute rejection of marrow grafts in mice. Dependence on and independence of functional TCR in the rejection process. J Immunol. 1994 May 1;152(9):4407–4416. [PubMed] [Google Scholar]
  34. Uematsu Y., Ryser S., Dembić Z., Borgulya P., Krimpenfort P., Berns A., von Boehmer H., Steinmetz M. In transgenic mice the introduced functional T cell receptor beta gene prevents expression of endogenous beta genes. Cell. 1988 Mar 25;52(6):831–841. doi: 10.1016/0092-8674(88)90425-4. [DOI] [PubMed] [Google Scholar]
  35. Vicari A., de Moraes M. do C., Gombert J. M., Dy M., Penit C., Papiernik M., Herbelin A. Interleukin 7 induces preferential expansion of V beta 8.2+CD4-8- and V beta 8.2+CD4+8- murine thymocytes positively selected by class I molecules. J Exp Med. 1994 Aug 1;180(2):653–661. doi: 10.1084/jem.180.2.653. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Yokoyama W. M. Natural killer cell receptors specific for major histocompatibility complex class I molecules. Proc Natl Acad Sci U S A. 1995 Apr 11;92(8):3081–3085. doi: 10.1073/pnas.92.8.3081. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Yoshimoto T., Paul W. E. CD4pos, NK1.1pos T cells promptly produce interleukin 4 in response to in vivo challenge with anti-CD3. J Exp Med. 1994 Apr 1;179(4):1285–1295. doi: 10.1084/jem.179.4.1285. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Zlotnik A., Godfrey D. I., Fischer M., Suda T. Cytokine production by mature and immature CD4-CD8- T cells. Alpha beta-T cell receptor+ CD4-CD8- T cells produce IL-4. J Immunol. 1992 Aug 15;149(4):1211–1215. [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES