Abstract
T LYMPHOCYTES are predisposed to recognition of foreign protein fragments bound to cell-surface molecules encoded by the major histocompatibility complex (MHC)1, 2. There is now compelling evidence that this specificity is a consequence of a selection process operating on developing T lymphocytes in the thymus3–6. As a result of this positive selection, thymocytes that express antigen receptors with a threshold affinity for self MHC-encoded glycoproteins preferentially emigrate from the thymus and seed peripheral lymphoid organs. The specificity for both foreign antigen and MHC molecules is imparted by the α and β chains of the T-cell antigen receptor (TCR)7, 8. Two other T-cell surface proteins, CD4 and CD8, which bind non-polymorphic regions of class II and class I MHC molecules respectively9, 10, are also involved in these recognition events and play an integral role in thymic selection. In order to elucidate the developmental pathways of class II MHC-rest rioted T cells in relation to these essential accessory molecules, we have produced TCR-transgenic mice expressing a receptor specific for a fragment of pigeon cytochrome c and the Ek (class II MHC) molecule. The transgenic TCR is expressed on virtually all T cells in mice expressing k. The thymuses of these mice contain an abnormally high percentage of mature CD4+CD8− cells. In addition, the peripheral T-cell population is almost exclusively CD4+, demonstrating that the MHC specificity of the TCR determines the phenotype of T cells during selection in the thymus.
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References
Babbitt, B., Allen, P. M., Matsueda, G., Haber, E. & Unanue, E. Nature 317, 359–361 (1985).
Buus, S., Sette, A., Colon, S. M., Miles, C. & Grey, H. M. Science 235, 1353–1358 (1987).
Zinkernagel, R. M. et al. J. exp. Med. 147, 884–896 (1978).
Bevan, M. J. Nature 269, 417–418 (1977).
Kisielow, P., Teh, H. S., Bluthmann, H. & von Boehmer, H. Nature 335, 730–733 (1988).
Sha, W. C. et al. Nature 336, 73–76 (1988).
Dembic, Z. et al. Nature 320, 232–238 (1986).
Saito, T., Weiss, A., Miller, J., Norcross, M. A. & Germain, R. N. Nature 325, 125–130 (1987).
Doyle, C. & Strominger, J. L. Nature 330, 256–259 (1987).
Norment, A.M., Salter, R. D., Parham, P., Engelhard, V.H. & Littman, D.R. Nature 336, 79–81 (1988).
Kronenberg, M., Siu, G., Hood, L. E. & Shastri, N. A. Rev. Immun. 4, 529–591 (1986).
Swain, S. L. Immun. Rev. 74, 129–142 (1983).
Saizawa, K., Rojo, J. & Janeway, C. A. Jr Nature 328, 260–263 (1987).
Marrack, P. et al. J. exp. Med. 158, 1077–1091 (1983).
Veillette, A., Bookman, M. A., Horak, E. M. & Bolen, J. B. Cell 55, 301–308 (1988).
Smith, L. Nature 326, 798–800 (1987).
Fowlkes, B. J., Schwartz, R. H. & Pardoll, D. M. Nature 334, 620–623 (1988).
Teh, H. S. et al. Nature 335, 229–233 (1988).
Sha, W. C. et al. Nature 335, 271–274 (1988).
Winoto, A. et al. Nature 324, 679–682 (1986).
Fink, P. J., Matis, L. A., McElligott, D. L., Bookman, M. & Hedrick, S. M. Nature 321, 219–226 (1986).
Hedrick, S. M. et al. Science 239, 1541–1544 (1988).
Roehm, N. et al. Cell 38, 577–584 (1984).
Pullen, A. M., Marrack, P. & Kappler, J. W. Nature 335, 796–801 (1988).
Berg, L. et al. Molec. cell. Biol. 8, 5459–5469 (1988).
Winoto, A. & Baltimore, D. EMBO J. 8, 729–733 (1989).
Kaye, J. & Hedrick, S. M. Nature 336, 580–583 (1988).
Krimpenfort, P. et al. EMBO J. 7, 745–750 (1988).
Hogan, B., Costantini, F. & Lacy, E. in Manipulating the Mouse Embryo (Cold Spring Harbor Laboratory, New York, 1987).
Leo, O., Foo, M., Sachs, D. H., Samelson, L. E. & Bluestone, J. A. Proc. natn. Acad. Sci. U.S.A. 84, 1374–1378 (1987).
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Kaye, J., Hsu, ML., Sauron, ME. et al. Selective development of CD4+ T cells in transgenic mice expressing a class II MHC-restricted antigen receptor. Nature 341, 746–749 (1989). https://doi.org/10.1038/341746a0
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DOI: https://doi.org/10.1038/341746a0
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