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Selective Expression of the 21-Kilodalton Tyrosine-Phosphorylated Form of TCR Promotes the Emergence of T Cells with Autoreactive Potential ¹

Lisa A. Pitcher^*, Meredith A. Mathis^*, Srividya Subramanian^*, Jennifer A. Young^*, Edward K. Wakeland^*, Paul E. Love and Nicolai S. C. van Oers^2,*,

^* Center for Immunology and Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, TX 75390; and National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892

T cells undergo negative selection in the thymus to eliminate potentially autoreactive cells. The signals generated through the TCR following receptor interactions with peptide/MHC complexes in the thymus control these selection processes. Following receptor ligation, a fraction of the TCR subunit appears as two distinct tyrosine-phosphorylated forms of 21 and 23 kDa (p21 and p23). Previous data have reported elevated levels of p21 in some murine models of autoimmunity. We have examined the contributions of both the p21 and p23 to T cell negative selection in the HY TCR-transgenic system using ITAM-substituted TCR and CD3 transgenic mice. Expression of just p21, in the absence of p23, partially impairs negative selection of self-reactive HY-specific T cells. This results in the emergence of potentially autoreactive peripheral T cells and an elevated population of CD11b⁺B220⁺ B cells in the spleen. These data clearly identify a specific and unique role for p21 during negative selection.

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