| First Author | Bettini ML | Year | 2014 |
| Journal | J Immunol | Volume | 193 |
| Issue | 1 | Pages | 258-67 |
| PubMed ID | 24899501 | Mgi Jnum | J:312760 |
| Mgi Id | MGI:6790294 | Doi | 10.4049/jimmunol.1400322 |
| Citation | Bettini ML, et al. (2014) Membrane association of the CD3epsilon signaling domain is required for optimal T cell development and function. J Immunol 193(1):258-67 |
| abstractText | The TCR:CD3 complex transduces signals that are critical for optimal T cell development and adaptive immunity. In resting T cells, the CD3epsilon cytoplasmic tail associates with the plasma membrane via a proximal basic-rich stretch (BRS). In this study, we show that mice lacking a functional CD3epsilon-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 CD3epsilon-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 CD3epsilon signaling domain is required for optimal thymocyte development and peripheral T cell function. |
