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Basal and antigen-induced exposure of the proline-rich sequence in CD3?.


ABSTRACT: The CD3? 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 (CD3?c) is currently unresolved. Furthermore, the extent to which a cis-acting CD3? 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, CD3? 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 CD3?c and prolonged accessibility of the CD3? PRS to Nck.

SUBMITTER: de la Cruz J 

PROVIDER: S-EPMC3810001 | biostudies-literature | 2011 Feb

REPOSITORIES: biostudies-literature

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Basal and antigen-induced exposure of the proline-rich sequence in CD3ε.

de la Cruz Javier J   Kruger Travis T   Parks Christopher A CA   Silge Robert L RL   van Oers Nicolai S C NS   Luescher Immanuel F IF   Schrum Adam G AG   Gil Diana D  

Journal of immunology (Baltimore, Md. : 1950) 20110112 4


The CD3ε 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 (CD3Δc) is currently unresolved. Furthermore, the extent to which a cis-acting CD3ε basic amino acid-rich stretch (BRS), with its unique p  ...[more]

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