| First Author | de la Cruz J | Year | 2011 |
| Journal | J Immunol | Volume | 186 |
| Issue | 4 | Pages | 2282-90 |
| PubMed ID | 21228347 | Mgi Jnum | J:169167 |
| Mgi Id | MGI:4939968 | Doi | 10.4049/jimmunol.1003225 |
| Citation | de la Cruz J, et al. (2011) Basal and antigen-induced exposure of the proline-rich sequence in CD3 (epsilon). J Immunol 186(4):2282-90 |
| abstractText | The CD3epsilon cytoplasmic tail contains a conserved proline-rich sequence (PRS) that influences TCR-CD3 expression and signaling. Although the PRS can bind the SH3.1 domain of the cytosolic adapter Nck, whether the PRS is constitutively available for Nck binding or instead represents a cryptic motif that is exposed via conformational change upon TCR-CD3 engagement (CD3Deltac) is currently unresolved. Furthermore, the extent to which a cis-acting CD3epsilon basic amino acid-rich stretch (BRS), with its unique phosphoinositide-binding capability, might impact PRS accessibility is not clear. In this study, we found that freshly harvested primary thymocytes expressed low to moderate basal levels of Nck-accessible PRS ('open-CD3'), although most TCR-CD3 complexes were inaccessible to Nck ('closed-CD3'). Ag presentation in vivo induced open-CD3, accounting for half of the basal level found in thymocytes from MHC(+) mice. Additional stimulation with either anti-CD3 Abs or peptide-MHC ligands further elevated open-CD3 above basal levels, consistent with a model wherein antigenic engagement induces maximum PRS exposure. We also found that the open-CD3 conformation induced by APCs outlasted the time of ligand occupancy, marking receptors that had been engaged. Finally, CD3epsilon BRS-phosphoinositide interactions played no role in either adoption of the initial closed-CD3 conformation or induction of open-CD3 by Ab stimulation. Thus, a basal level of open-CD3 is succeeded by a higher, induced level upon TCR-CD3 engagement, involving CD3Deltac and prolonged accessibility of the CD3epsilon PRS to Nck. |
