Matthew L Bettini, Clifford Guy, Pradyot Dash, Kate M Vignali, David E Hamm, Jessica Dobbins, Etienne Gagnon, Paul G Thomas, Kai W Wucherpfennig, Dario A A Vignali
Journal of immunology (Baltimore, Md. : 1950) 2014 Jul 01The TCR:CD3 complex transduces signals that are critical for optimal T cell development and adaptive immunity. In resting T cells, the CD3ε cytoplasmic tail associates with the plasma membrane via a proximal basic-rich stretch (BRS). In this study, we show that mice lacking a functional CD3ε-BRS exhibited substantial reductions in thymic cellularity and limited CD4- CD8- double-negative (DN) 3 to DN4 thymocyte transition, because of enhanced DN4 TCR signaling resulting in increased cell death and TCR downregulation in all subsequent populations. Furthermore, positive, but not negative, T cell selection was affected in mice lacking a functional CD3ε-BRS, which led to limited peripheral T cell function and substantially reduced responsiveness to influenza infection. Collectively, these results indicate that membrane association of the CD3ε signaling domain is required for optimal thymocyte development and peripheral T cell function. Copyright © 2014 by The American Association of Immunologists, Inc.
Matthew L Bettini, Clifford Guy, Pradyot Dash, Kate M Vignali, David E Hamm, Jessica Dobbins, Etienne Gagnon, Paul G Thomas, Kai W Wucherpfennig, Dario A A Vignali. Membrane association of the CD3ε signaling domain is required for optimal T cell development and function. Journal of immunology (Baltimore, Md. : 1950). 2014 Jul 01;193(1):258-67
PMID: 24899501
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