tetano
Editor, Senior Moderator
J Immunol. 2014 Jun 4. pii: 1400322. [Epub ahead of print]
Membrane Association of the CD3ε Signaling Domain Is Required for Optimal T Cell Development and Function.
Bettini ML1, Guy C1, Dash P1, Vignali KM1, Hamm DE2, Dobbins J3, Gagnon E3, Thomas PG1, Wucherpfennig KW3, Vignali DA4.
Author information
Abstract
The 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.
PMID:
24899501
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/24899501
Membrane Association of the CD3ε Signaling Domain Is Required for Optimal T Cell Development and Function.
Bettini ML1, Guy C1, Dash P1, Vignali KM1, Hamm DE2, Dobbins J3, Gagnon E3, Thomas PG1, Wucherpfennig KW3, Vignali DA4.
Author information
Abstract
The 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.
PMID:
24899501
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/24899501