Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter
  • Published:

Defective T-cell receptor signalling and positive selection of Vav-deficient CD4+CDS+thymocytes

Nature volume 374, pages 474–476 (1995)Cite this article

Abstract

DURING lymphocyte development, cellular proliferation and posi-tive and negative selection events ensure the production of T and B lymphocytes bearing highly diverse, but self-tolerant, repertoires of antigen receptors1,2. These processes are initiated when engage-ment of growth-factor receptors, or the T3,4 and B5 lymphocyte antigen receptors, induces tyrosine phosphorylation of specific SH2- and SH3-domain-containing cytoplasmic proteins, including Vav3,6,7. Here we show that vav-/- embryonic stem cells generate only limited numbers of immature and mature T and B lympho-cytes in the RAG-2 blastocyst complementation assay8. Further-inore, Vav-deficient T lymphocytes showed severely unpaired antigen receptor signalling. Finally, we demonstrate that Vav-dependent signalling pathways regulate maturation, but not CD4/ CD8 lineage commitment, during T-cell-receptor-mediated positive selection of immature CD4 + CD8 + precursors into mature CD4 + CD8- or CD4-CD8+ T cells.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. von Boehmer, H. Cell 76, 219–228 (1994).

    Article  CAS  PubMed  Google Scholar 

  2. Nossal, G. J. V. Cell 76, 229–239 (1994).

    Article  CAS  PubMed  Google Scholar 

  3. Bustelo, X. R., Ledbetter, J. A. & Barbacid, M. Nature 356, 68–71 (1992).

    Article  ADS  CAS  PubMed  Google Scholar 

  4. Margolis, B. et al. Nature 356, 71–74 (1992).

    Article  ADS  CAS  PubMed  Google Scholar 

  5. Bustelo, X. R. & Barbacid, M. Science 256, 1196–1199 (1992).

    Article  ADS  CAS  PubMed  Google Scholar 

  6. Katzav, S., Martin-Zanca, D. & Barbacid, M. EMBO J. 8, 2283–2290 (1989).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Adams, J. M., Houston, H., Allen, J., Lints, T. & Harvey, R. Oncogene 7, 611–618 (1992).

    CAS  PubMed  Google Scholar 

  8. Chen, J., Lansford, R., Stewart, V., Young, F. & Alt, F. W. Proc. natn. Acad. Sci. USA 90, 4528–4532 (1993).

    Article  ADS  CAS  Google Scholar 

  9. Zmuidzinas, A. et al. EMBO J. 14, 1–11 (1995).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Dosil, M., Wang, S. & Lemischka, I. R. Molec. cell. Biol. 13, 6572–6585 (1993).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Godfrey, D., Zlotnik, A. & Suda, T. J. Immun. 149, 2281–2285 (1992).

    CAS  PubMed  Google Scholar 

  12. Rolink, A., Streb, M., Nishikawa, S.-I. & Melchers, F. Eur. J. Immun. 21, 2609–2612 (1991).

    Article  CAS  Google Scholar 

  13. Robey, E. & Fowlkes, B. J. A. Rev. Immun. 12, 675–705 (1994).

    Article  CAS  Google Scholar 

  14. Guidos, C. J., Danska, J. S., Fathman, C. G. & Weissman, I. L. J. exp. Med. 172, 835–845 (1990).

    Article  CAS  PubMed  Google Scholar 

  15. Davis, C. B., Killeen, N., Crooks, M. E. C., Raulet, D. & Littman, D. R. Cell 73, 237–247 (1993).

    Article  CAS  PubMed  Google Scholar 

  16. Chan, S. H., Cosgrove, D., Waltzinger, C., Benoist, C., & Mathis, D. Cell 73, 225–236 (1993).

    Article  CAS  PubMed  Google Scholar 

  17. van Meerwijk, J. P. M. & Germain, R. N. Science 261, 911–915 (1993).

    Article  ADS  CAS  PubMed  Google Scholar 

  18. Guidos, C. J. & Weissman, I. L. in Molecular Mechanisms of Immunological Self-recognition (eds Alt, F. & Vogel, H. J.) 137–147 (Academic, San Diego, 1993).

    Google Scholar 

  19. Bendelac, A., Matzinger, P., Seder, R. A., Paul, W. E. & Schwartz, R. H. J. exp. Med 175, 731–742 (1992).

    Article  CAS  PubMed  Google Scholar 

  20. Ashton-Rickardt, P. G. & Tonegawa, S. Immun. Today 15, 362–365 (1994).

    Article  CAS  PubMed  Google Scholar 

  21. Weiss, A. & Littman, D. R. Cell 76, 263–274 (1994).

    Article  CAS  PubMed  Google Scholar 

  22. Gulbins, E. et al. Science 260, 822–824 (1993).

    Article  ADS  CAS  PubMed  Google Scholar 

  23. Boguski, M. S. & McCormick, F. Nature 366, 643–654 (1993).

    Article  ADS  CAS  PubMed  Google Scholar 

  24. Molina, T. J. et al. Nature 357, 161–164 (1992).

    Article  ADS  CAS  PubMed  Google Scholar 

  25. Mombaerts, P., Anderson, S. J., Perlmutter, R. M., Mak, T. W. & Tonegawa, S. Immunity 1, 261–267 (1994).

    Article  CAS  PubMed  Google Scholar 

  26. Arpaia, E., Shahar, M., Dadi, H., Cohen, A. & Roifman, C. Cell 76, 947–958 (1994).

    Article  CAS  PubMed  Google Scholar 

  27. Chan, A. et al. Science 264, 1599–1601 (1994).

    Article  ADS  CAS  PubMed  Google Scholar 

  28. Elder, M. et al. Science 264, 1596–1599 (1994).

    Article  ADS  CAS  PubMed  Google Scholar 

  29. Kishihara, K. et al. Cell 74, 143–156 (1993).

    Article  CAS  PubMed  Google Scholar 

  30. Danska, J. S. et al. Science 266, 450–455 (1994).

    Article  ADS  CAS  PubMed  Google Scholar 

Download references

Author information

Author notes

  1. Antanina Zmuidzinas

    Present address: EPG Research Foundation, Manhasset, New York, 11030, USA

Authors and Affiliations

  1. Program in Molecular Biology and Cancer, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, Ontario, M5G 1X5, Canada

    Klaus-Dieter Fischer, Sandra Gardner & Alan Bernstein

  2. Department of Molecular and Medical Genetics, University of Toronto, Toronto, Ontario, M5S 1A1, Canada

    Klaus-Dieter Fischer, Sandra Gardner & Alan Bernstein

  3. Department of Molecular Biology, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey, 08543-4000, USA

    Antanina Zmuidzinas & Mariano Barbacid

  4. Division of Immunology and Cancer, Hospital for Sick Children Research Institute, 555 University Avenue, Toronto, Ontario, Canada, M5G 1X8

    Cynthia Guidos

  5. Department of Immunology, University of Toronto, Toronto, Ontario, M5S 1A1, Canada

    Cynthia Guidos

Authors
  1. Klaus-Dieter Fischer
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Antanina Zmuidzinas
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sandra Gardner
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Mariano Barbacid
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Alan Bernstein
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Cynthia Guidos
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Fischer, KD., Zmuidzinas, A., Gardner, S. et al. Defective T-cell receptor signalling and positive selection of Vav-deficient CD4+CDS+thymocytes. Nature 374, 474–476 (1995). https://doi.org/10.1038/374474a0

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/374474a0

This article is cited by

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing