| First Author | Jiang N | Year | 2011 |
| Journal | Immunity | Volume | 34 |
| Issue | 1 | Pages | 13-23 |
| PubMed ID | 21256056 | Mgi Jnum | J:168063 |
| Mgi Id | MGI:4881839 | Doi | 10.1016/j.immuni.2010.12.017 |
| Citation | Jiang N, et al. (2011) Two-Stage Cooperative T Cell Receptor-Peptide Major Histocompatibility Complex-CD8 Trimolecular Interactions Amplify Antigen Discrimination. Immunity 34(1):13-23 |
| abstractText | The T cell receptor (TCR) and CD8 bind peptide-major histocompatibility complex (pMHC) glycoproteins to initiate adaptive immune responses, yet the trimolecular binding kinetics at the T cell membrane is unknown. By using a micropipette adhesion frequency assay, we show that this kinetics has two stages. The first consists of TCR-dominant binding to agonist pMHC. This triggers a second stage consisting of a step increase in adhesion after a one second delay. The second-stage binding requires Src family kinase activity to initiate CD8 binding to the same pMHC engaged by the TCR. This induced trimeric-cooperative interaction enhances adhesion synergistically to favor potent ligands, which further amplifies discrimination. Our data reveal a TCR-CD8 positive-feedback loop involved in initial signaling steps that is sensitive to a single pMHC is rapid, reversible, synergistic, and peptide discriminative. |
