| First Author | Roy E | Year | 2010 |
| Journal | Proc Natl Acad Sci U S A | Volume | 107 |
| Issue | 35 | Pages | 15529-34 |
| PubMed ID | 20709959 | Mgi Jnum | J:163665 |
| Mgi Id | MGI:4829408 | Doi | 10.1073/pnas.1009743107 |
| Citation | Roy E, et al. (2010) Nck adaptors are positive regulators of the size and sensitivity of the T-cell repertoire. Proc Natl Acad Sci U S A 107(35):15529-34 |
| abstractText | The size and sensitivity of the T-cell repertoire governs the effectiveness of immune responses against invading pathogens. Both are modulated by T-cell receptor (TCR) activity through molecular mechanisms, which remain unclear. Here, we provide genetic evidence that the SH2/SH3 domain containing proteins Nck lower the threshold of T-cell responsiveness. The hallmarks of Nck deletion were T-cell lymphopenia and hyporeactivity to TCR-mediated stimulation. In the absence of the Nck adaptors, peripheral T cells expressing a TCR with low avidity for self-antigens were strongly reduced, whereas an overall impairment of T-cell activation by weak antigenic stimulation was observed. Mechanistically, Nck deletion resulted in a significant decrease in calcium mobilization and ERK phosphorylation upon TCR engagement. Taken together, our findings unveil a crucial role for the Nck adaptors in shaping the T-cell repertoire to ensure maximal antigenic coverage and optimal T cell excitability. |
