| First Author | Borroto A | Year | 2014 |
| Journal | J Immunol | Volume | 192 |
| Issue | 5 | Pages | 2042-53 |
| PubMed ID | 24470497 | Mgi Jnum | J:209827 |
| Mgi Id | MGI:5568798 | Doi | 10.4049/jimmunol.1203414 |
| Citation | Borroto A, et al. (2014) Relevance of Nck-CD3 epsilon interaction for T cell activation in vivo. J Immunol 192(5):2042-53 |
| abstractText | On TCR ligation, the adaptor Nck is recruited through its src homology 3.1 domain to a proline-rich sequence (PRS) in CD3epsilon. We have studied the relevance of this interaction for T cell activation in vitro and in vivo by targeting the interaction sites in both partners. The first approach consisted of studying a knockin (KI) mouse line (KI-PRS) bearing a conservative mutation in the PRS that makes the TCR incompetent to recruit Nck. This deficiency prevents T cell activation by Ag in vitro and inhibited very early TCR signaling events including the tyrosine phosphorylation of CD3zeta. Most important, KI-PRS mice are partly protected against the development of neurological symptoms in an experimental autoimmune encephalitis model, and show a deficient antitumoral response after vaccination. The second approach consisted of using a high-affinity peptide that specifically binds the src homology 3.1 domain and prevents the interaction of Nck with CD3epsilon. This peptide inhibits T cell proliferation in vitro and in vivo. These data suggest that Nck recruitment to the TCR is fundamental to mount an efficient T cell response in vivo, and that the Nck-CD3epsilon interaction may represent a target for pharmacological modulation of the immune response. |
