| First Author | Van Laethem F | Year | 2013 |
| Journal | Cell | Volume | 154 |
| Issue | 6 | Pages | 1326-41 |
| PubMed ID | 24034254 | Mgi Jnum | J:204615 |
| Mgi Id | MGI:5532887 | Doi | 10.1016/j.cell.2013.08.009 |
| Citation | Van Laethem F, et al. (2013) Lck availability during thymic selection determines the recognition specificity of the T cell repertoire. Cell 154(6):1326-41 |
| abstractText | Thymic selection requires signaling by the protein tyrosine kinase Lck to generate T cells expressing alphabeta T cell antigen receptors (TCR). For reasons not understood, the thymus selects only alphabetaTCR that are restricted by major histocompatibility complex (MHC)-encoded determinants. Here, we report that Lck proteins that were coreceptor associated promoted thymic selection of conventionally MHC-restricted TCR, but Lck proteins that were coreceptor free promoted thymic selection of MHC-independent TCR. Transgenic TCR with MHC-independent specificity for CD155 utilized coreceptor-free Lck to signal thymic selection in the absence of MHC, unlike any transgenic TCR previously described. Thus, the thymus can select either MHC-restricted or MHC-independent alphabetaTCR depending on whether Lck is coreceptor associated or coreceptor free. We conclude that the intracellular state of Lck determines the specificity of thymic selection and that Lck association with coreceptor proteins during thymic selection is the mechanism by which MHC restriction is imposed on a randomly generated alphabetaTCR repertoire. |
