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Publication : Selective expression of the 21-kilodalton tyrosine-phosphorylated form of TCR zeta promotes the emergence of T cells with autoreactive potential.

First Author  Pitcher LA Year  2005
Journal  J Immunol Volume  174
Issue  10 Pages  6071-9
PubMed ID  15879101 Mgi Jnum  J:98983
Mgi Id  MGI:3580936 Doi  10.4049/jimmunol.174.10.6071
Citation  Pitcher LA, et al. (2005) Selective expression of the 21-kilodalton tyrosine-phosphorylated form of TCR zeta promotes the emergence of T cells with autoreactive potential. J Immunol 174(10):6071-9
abstractText  T cells undergo negative selection in the thymus to eliminate potentially autoreactive cells. The signals generated through the alphabeta TCR following receptor interactions with peptide/MHC complexes in the thymus control these selection processes. Following receptor ligation, a fraction of the TCR zeta 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 zeta and CD3 epsilon 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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