| First Author | Zhou RW | Year | 2014 |
| Journal | Nat Immunol | Volume | 15 |
| Issue | 11 | Pages | 1038-45 |
| PubMed ID | 25263124 | Mgi Jnum | J:259376 |
| Mgi Id | MGI:6142300 | Doi | 10.1038/ni.3007 |
| Citation | Zhou RW, et al. (2014) N-glycosylation bidirectionally extends the boundaries of thymocyte positive selection by decoupling Lck from Ca(2)(+) signaling. Nat Immunol 15(11):1038-45 |
| abstractText | Positive selection of diverse yet self-tolerant thymocytes is vital to immunity and requires a limited degree of T cell antigen receptor (TCR) signaling in response to self peptide-major histocompatibility complexes (self peptide-MHCs). Affinity of newly generated TCR for peptide-MHC primarily sets the boundaries for positive selection. We report that N-glycan branching of TCR and the CD4 and CD8 coreceptors separately altered the upper and lower affinity boundaries from which interactions between peptide-MHC and TCR positively select T cells. During thymocyte development, N-glycan branching varied approximately 15-fold. N-glycan branching was required for positive selection and decoupled Lck signaling from TCR-driven Ca(2+) flux to simultaneously promote low-affinity peptide-MHC responses while inhibiting high-affinity ones. Therefore, N-glycan branching imposes a sliding scale on interactions between peptide-MHC and TCR that bidirectionally expands the affinity range for positive selection. |
