Haopeng Wang, Jeff Holst, Seng-Ryong Woo, Cliff Guy, Matt Bettini, Yao Wang, Aaron Shafer, Mayumi Naramura, Michaël Mingueneau, Leonard L Dragone, Sandra M Hayes, Bernard Malissen, Hamid Band, Dario A A Vignali
Expression of the T-cell receptor (TCR):CD3 complex is tightly regulated during T-cell development. The mechanism and physiological role of this regulation are unclear. Here, we show that the TCR:CD3 complex is constitutively ubiquitylated in immature double positive (DP) thymocytes, but not mature single positive (SP) thymocytes or splenic T cells. This steady state, tonic CD3 monoubiquitylation is mediated by the CD3varepsilon proline-rich sequence, Lck, c-Cbl, and SLAP, which collectively trigger the dynamin-dependent downmodulation, lysosomal sequestration and degradation of surface TCR:CD3 complexes...
April 7, 2010: EMBO Journal