Dynamic Tuning of T Cell Reactivity by Self-Peptide-Major Histocompatibility Complex Ligands

doi:10.1084/jem.193.10.1179

Published online 21 May 2001.

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© The Rockefeller University Press, 0022-1007/2001/5/1179/ $5.00
The Journal of Experimental Medicine, Volume 193, Number 10, May 21, 2001 1179-1188

Original Article

Dynamic Tuning of T Cell Reactivity by Self-Peptide–Major Histocompatibility Complex Ligands

Phillip Wong^a, Gregory M. Barton^a, Katherine A. Forbush^a, and Alexander Y. Rudensky^a
^a Department of Immunology and Howard Hughes Medical Institute, University of Washington School of Medicine, Seattle,Washington 98195

Correspondence to: Alexander Y. Rudensky, Box 357370, Howard Hughes Medical Institute, Department of Immunology, University of Washington School of Medicine, Seattle, WA 98195. Tel:206-685-7644 Fax:206-685-3612 E-mail:aruden{at}u.washington.edu.

Intrathymic self-peptide–major histocompatibility complexclass II (MHC) molecules shape the T cell repertoire throughpositive and negative selection of immature CD4⁺CD8⁺ thymocytes.By analyzing the development of MHC class II–restrictedT cell receptor (TCR) transgenic T cells under conditions inwhich the endogenous peptide repertoire is altered, we showthat self-peptide–MHC complexes are also involved in settingT cell activation thresholds. This occurs through changes inthe expression level of molecules on thymocytes that influencethe sensitivity of TCR signaling. Our results suggest that theendogenous peptide repertoire modulates T cell responsivenessin the thymus in order to enforce tolerance to self-antigens.

Key Words: T cell antigen receptors, thymus, tolerance, transgenic mice,CD5

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