Abstract
THE developmental fate of immature thymocytes is determined by the specificity of their T-cell antigen receptors (TCRs). Immature CD4+8+ thymocytes are positively selected to differentiate into mature T cells1–6 by recognition of peptides associated with major histocompatibility complex (MHC) encoded molecules7–10 on thymic epithelial cells11–14. But neither the identity of molecules transducing positive selection signals nor the nature of the signals themselves is fully known. Here we report that direct ligation of TCR molecules by monoclonal antibodies specific for either clonotypic or CD3 chains can signal immature thymocytes to differentiate into mature CD4+8− T cells, even in the absence of MHC expression and MHC-dependent CD4 coreceptor signalling. Moreover, we show that TCR engagement induces positive selection signals only in the absence of TCR aggregation and that TCR aggregation is inhibitory for positive selection. Thus, low valency of TCR crosslinking is a critical parameter15, distinguishing positive selection from other TCR-mediated signalling events.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 51 print issues and online access
$199.00 per year
only $3.90 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Teh, H. S. et al. Nature 335, 229–233 (1988).
Sha, W. C. et al. Nature 336, 73–76 (1988).
Berg, L. J. et al. Cell 58, 1035–1046 (1989).
Pircher, H., Burki, K., Lang, R., Hengartner, H. & Zinkernagel, R. M. Nature 342, 559–561 (1989).
Blackman, M., Kappler, J. & Marrack, P. Science 248, 1335–1341 (1990).
Kaye, J. & Fllenberger, D. L. Cell 71, 423–435 (1992).
Ashton-Rickardt, P. G., van Kaer, L., Schumacher, T. N. M., Pleogh, H. L. & Tonegawa, S. Cell 73, 1041–1049 (1993).
Hogquist, K. A. et al. Cell 76, 17–27 (1994).
Ashton-Rickardt, P. G. et al. Cell 76, 651–663 (1994).
Sebzda, E. et al. Science 263, 1615–1618 (1994).
Lo, D. & Sprent, J. Nature 319, 672–675 (1986).
Vukmanovic, S., Grandea, A. G., Faas, S. J., Knowles, B. B. & Bevan, M. J. Nature 359, 729–732 (1992).
Hugo, P., Kappler, J. W., Godfrey, D. I. & Marrack, P. C. Nature 360, 679–682 (1992).
Anderson, G., Jenkinson, E. J., Moore, N. C. & Owen, J. J. T. Nature 362, 70–73 (1993).
Dintzis, H. M., Dintzis, R. Z. & Vogelstein, B. Proc. natn. Acad. Sci. U. S. A. 73, 3671–3675 (1976).
Cosgrove, D. et al. Cell 66, 1051–1066 (1991).
Grusby, M. J., Johnson, R. S., Papaioannou, V. E. & Glimcher, L. H. Science 253, 1417–1420 (1991).
Muller, K. P. & Kyewski, B. A. Eur. J. Immun. 23, 1661–1670 (1993).
Chan, S., Cosgrove, D., Watzinger, C., Benoist, C. & Mathis, D. Cell 73, 225–236 (1993).
Grusby, M. J. et al. Proc. natn. Acad. Sci. U. S. A. 90, 3913–3917 (1993).
Coulie, P. G. et al. Eur. J. Immun. 21, 1703–1709 (1991).
Hunig, T. Eur. J. Immun. 18, 2089–2092 (1988).
Takahama, Y. & Singer, A. Science 258, 1456–1462 (1992).
Smith, C. A., Williams, C. T., Kingston, R., Jenkinson, E. J. & Owen, J. J. T. Nature 337, 181–184 (1989).
McConkey, D. J., Hartzell, P., Amador-Perez, J. F., Orrenius, S. & Jondal, M. J. Immun. 143, 1801–1806 (1989).
Murphy, K. M., Heimberger, A. B. & Loh, D. Y. Science 250, 1720–1722 (1990).
Nakayama, T. et al. Proc. natn. Acad. Sci. U.S.A. 88, 9949–9953 (1991).
Punt, J. A., Roberts, J. L., Kearse, K. P. & Singer, A. J. exp. Med. 180, 587–593 (1994).
Leo, O., Foo, M., Sachs, D. H., Samelson, L. E. & Bluestone, J. A. Proc. natn. Acad. Sci. U.S.A. 84, 1374–1378 (1987).
Blumberg, R. et al. Proc. natn. Acad. Sci. U.S.A. 87, 7220–7224 (1990).
de la Hera, A., Muller, U., Olsson, C., Isaazs, S. & Tunnacliffe, A. J. exp. Med. 173, 7–17 (1991).
McDuffie, M., Born, W., Marrack, P. & Kappler, J. Proc. natn. Acad. Sci. U. S. A. 83, 8728–8732 (1986).
Born, W. et al. J. Immun. 138, 999–1008 (1987).
Finkel, T. H. et al. Cell 58, 1047–1054 (1989).
Yachelini, P., Falk, I. & Eichmann, K. J. Immun. 145, 1382–1389 (1990).
Punt, J. A., Hosono, M. & Hashimoto, Y. J. Immun. 151, 1290–1302 (1993).
Killeen, N. & Littman, D. R. Nature 364, 729–732 (1993).
Swain, S. L. Immun. Rev. 74, 129–142 (1983).
Doyle, C. & Strominger, J. L. Nature 330, 256–259 (1987).
Singer, A., Mizuochi, T., Munitz, T. I. & Gress, R. E. in Progress in Immunology VI (eds Cinader, B. & Miller, R. G. ) 60–66 (Academic, New York, 1986).
Singer, A., Munitz, T. I. & Gress, R. E. Transplant Proc. 19, 107–110 (1987).
Marrack, P., McCormack, J. & Kappler, J. Nature 338, 503–505 (1989).
Kourilsky, P. & Claverie, J. M. Cell 56, 327–329 (1989).
Kubo, R. T., Born, W., Kappler, J. W., Marrack, P. & Pigeon, M. J. Immun. 142, 2736–2742 (1989).
Robinson, J. H. & Owen, J. J. T. Clin. Exp. Immun. 27, 322–327 (1976).
Mandel, T. E. & Kennedy, M. M. Immunology 35, 317–331 (1978).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Takahama, Y., Suzuki, H., Katz, K. et al. Positive selection of CD4+T cells by TCR ligation without aggregation even in the absence of MHC. Nature 371, 67–70 (1994). https://doi.org/10.1038/371067a0
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/371067a0
This article is cited by
-
Cytokine-free directed differentiation of human pluripotent stem cells efficiently produces hemogenic endothelium with lymphoid potential
Stem Cell Research & Therapy (2017)
-
Thymic epithelial cells: antigen presenting cells that regulate T cell repertoire and tolerance development
Immunologic Research (2012)
-
Signaling by intrathymic cytokines, not T cell antigen receptors, specifies CD8 lineage choice and promotes the differentiation of cytotoxic-lineage T cells
Nature Immunology (2010)
-
Ligand-specific oligomerization of T-cell receptor molecules
Nature (1997)
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.