Figure 3

Suggested model for the function of the CD3ε PRS in double-positive thymocytes. (A) Nck associates with CD3ε in the absence of pMHC and recruits Lck, which phosphorylates TCRζ. Subsequently, phosphorylated TCRζ recruits SLAP, and SLAP-associated c-Cbl ubiquitinates (Ub) TCRζ. This leads to the degradation of TCRζ and thus increases the TCR sampling rate. (B) pMHC-mediated ligation of the TCR results in more complete phosphorylation of the CD3 ITAMS. In this context, the interaction of CD3ε-bound Nck with Lck may be necessary to prime the system and allow CD4 coreceptor-dependent Lck to initiate a full activation response with phosphorylation of the CD3ε ITAMS. This results in the recruitment of ZAP70, the dissociation of Nck and SLAP and thus the stabilization of TCR surface expression. (Figure accords with models suggested in [59]).