| First Author | Van Laethem F | Year | 2007 |
| Journal | Immunity | Volume | 27 |
| Issue | 5 | Pages | 735-50 |
| PubMed ID | 18023370 | Mgi Jnum | J:127623 |
| Mgi Id | MGI:3763996 | Doi | 10.1016/j.immuni.2007.10.007 |
| Citation | Van Laethem F, et al. (2007) Deletion of CD4 and CD8 Coreceptors Permits Generation of alphabetaT Cells that Recognize Antigens Independently of the MHC. Immunity 27(5):735-50 |
| abstractText | The thymus generates major histocompatibility complex (MHC)-restricted alphabetaT cells that only recognize antigenic ligands in association with MHC or MHC-like molecules. We hypothesized that MHC specificity might be imposed on a broader alphabetaTCR repertoire during thymic selection by CD4 and CD8 coreceptors that bind and effectively sequester the tyrosine kinase Lck, thereby preventing T cell receptor (TCR) signaling by non-MHC ligands that do not engage either coreceptor. This hypothesis predicts that, in coreceptor-deficient mice, alphabeta thymocytes would be signaled by non-MHC ligands to differentiate into alphabetaT cells lacking MHC specificity. We now report that MHC-independent alphabetaT cells were indeed generated in mice deficient in both coreceptors as well as MHC ('quad-deficient' mice) and that such mice contained a diverse alphabetaT cell repertoire whose MHC independence was confirmed at the clonal level. We conclude that CD4 and CD8 coreceptors impose MHC specificity on a broader alphabetaTCR repertoire during thymic selection by preventing thymocytes from being signaled by non-MHC ligands. |
