On the dynamics of TCR : CD3 complex cell surface expression and downmodulation

TCR downmodulation following ligation by MHC:peptide complexes is considere d to be a pivotal event in T cell activation. Here, we analyzed the dynamic s of TCR:CD3 cell surface expression on resting and antigen-activated T cel ls. We show that the TCR:CD3 complex is very stable and is rapidly internal ized and recycled in resting T cells. Surprisingly, the internalization rat e is not increased following TCR ligation by MHC:peptide complexes, despite significant TCR downmodulation, suggesting that constitutive internalizati on rather than ligation-induced downmodulation serves as the force that dri ves serial ligation. Furthermore, TCR downmodulation is mediated by the int racellular retention of ligated complexes and degradation by lysosomes and proteasomes. Thus, our data demonstrate that ligation induces TCR downmodul ation by preventing recycling rather than inducing internalization.