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The Journal of Immunology, 2007, 178: 4120-4128.
Copyright © 2007 by The American Association of Immunologists, Inc.

The Constitutive Tyrosine Phosphorylation of CD3{zeta} Results from TCR-MHC Interactions That Are Independent of Thymic Selection1

Amy M. Becker*, Laura M. DeFord-Watts*, Christoph Wuelfing* and Nicolai S. C. van Oers2,*,{dagger}

* Department of Immunology and {dagger} Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, TX 75390

The TCR complex, when isolated from thymocytes and peripheral T cells, contains a constitutively tyrosine-phosphorylated CD3{zeta} molecule termed p21. Previous investigations have shown that the constitutive phosphorylation of CD3{zeta} results from TCR interactions with MHC molecules occurring in both the thymus and the periphery. To determine what contribution the selection environment had on this constitutive phosphorylation, we analyzed CD3{zeta} from several distinct class I- and II-restricted TCR-transgenic mice where thymocyte development occurred in either a selecting or a nonselecting MHC environment. Herein, we report that constitutively phosphorylated CD3{zeta} (p21) was present in thymocytes that developed under nonselecting peptide-MHC conditions. These findings strongly support the model that the TCR has an inherent avidity for MHC molecules before repertoire selection. Biochemical analyses of the TCR complex before and after TCR stimulation suggested that the constitutively phosphorylated CD3{zeta} subunit did not contribute to de novo TCR signals. These findings may have important implications for T cell functions during self-MHC recognition under normal and autoimmune circumstances.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

1 This work was supported by National Institutes of Health Grant AI42953 (to N.S.C.v.O.) and National Institutes of Health Training Grant NIH 5T 32 AI005284 (to L.M.D.-W. and A.M.B.).

2 Address correspondence and reprint requests to Dr. Nicolai S. C. van Oers, Department of Immunology, University of Texas Southwestern Medical Center, 6000 Harry Hines Boulevard, Dallas, TX 75390. E-mail address: nicolai.vanoers{at}utsouthwestern.edu

3 Abbreviations used in this paper: beta2m, beta2-microglobulin; CD62L, L-selectin.







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