Membrane Association of the CD3 epsilon Signaling Domain Is Required for Optimal T Cell Development and Function

作者：Bettini Matthew L; Guy Clifford; Dash Pradyot; Vignali Kate M; Hamm David E; Dobbins Jessica; Gagnon Etienne; Thomas Paul G; Wucherpfennig Kai W; Vignali Dario A A^*

来源：The Journal of Immunology, 2014, 193(1): 258-267.

DOI：10.4049/jimmunol.1400322

The TCR:CD3 complex transduces signals that are critical for optimal T cell development and adaptive immunity. In resting T cells, the CD3 cytoplasmic tail associates with the plasma membrane via a proximal basic-rich stretch (BRS). In this study, we show that mice lacking a functional CD3 epsilon-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 CD3 epsilon-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 CD3 signaling domain is required for optimal thymocyte development and peripheral T cell function.

• 出版日期2014-7-1