The Journal of Experimental Medicine
IN Cell Analyzer 2000
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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 Wonga, Gregory M. Bartona, Katherine A. Forbusha, and Alexander Y. Rudenskya

a Department of Immunology and Howard Hughes Medical Institute, University of Washington School of Medicine, Seattle,Washington 98195
Box 357370, Howard Hughes Medical Institute, Department of Immunology, University of Washington School of Medicine, Seattle, WA 98195.206-685-3612206-685-7644

aruden{at}u.washington.edu

Intrathymic self-peptide–major histocompatibility complex class II (MHC) molecules shape the T cell repertoire through positive and negative selection of immature CD4+CD8+ thymocytes. By analyzing the development of MHC class II–restricted T cell receptor (TCR) transgenic T cells under conditions in which the endogenous peptide repertoire is altered, we show that self-peptide–MHC complexes are also involved in setting T cell activation thresholds. This occurs through changes in the expression level of molecules on thymocytes that influence the sensitivity of TCR signaling. Our results suggest that the endogenous peptide repertoire modulates T cell responsiveness in the thymus in order to enforce tolerance to self-antigens.

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

Abbreviations used in this paper: APC, allophycocyanin; β2m, β2-microglobulin; CLIP, class II–associated Ii peptide; DP, double positive; Ii, invariant chain; PerCP, peridinin chlorophyll protein; RAG, recombination activating gene; SP, single positive.

© 2001 The Rockefeller University Press


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