Internalization and intracellular fate of TCR-CD3 complexes.
The number of surface TCR-CD3 complexes is maintained by an equilibrium between the synthesis and secretion of new polypeptides, their internalization, recycling, and degradation. The different subunits of the TCR-CD3 complex do not display the same intracellular trafficking dynamics. Thus, in the absence of stimuli, TCR and zeta chains may be degraded at a higher rate than CD3 subunits, which are mostly recycled. T-cell activation by antigen, anti-TCR-CD3 antibodies, or pharmacological activators of protein kinase C, results in increased TCR-CD3 internalization, followed by the downmodulation of TCR-CD3 surface levels. Once internalized, TCR-CD3 complexes may either enter a recycling pathway or be sorted to lysosomes and degraded. Protein serine kinases and protein tyrosine kinases may influence the internalization and intracellular sorting of TCR-CD3 complexes. In line with these results TCR-CD3 ligands stimulate both TCR-CD3 internalization and degradation, whereas protein kinase C activators stimulate internalization only. Depending on the stimulus applied, internalization motifs from one or several TCR-CD3 subunits mediate endocytic routing of the complex. The involvement of signaling molecules in the intracellular fate of TCR-CD3, the nature and location of sequences for internalization and intracellular sorting, and the role of downregulation in T-cell activation are still the main open questions.
Alcover
A
A
Unité de Biologie des Interactions Cellulaires, CNRS, URA 1960, Institut Pasteur, Paris, France.
Alarcón
B
B
D000818:Animals; D015536:Down-Regulation; D004705:Endocytosis; D006207:Half-Life; D006801:Humans; D008213:Lymphocyte Activation; D010766:Phosphorylation; D011493:Protein Kinase C / Q000502:physiology; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000378:metabolism*; D012694:Serine / Q000378:metabolism; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000378:metabolism
D017260:Receptor-CD3 Complex, Antigen, T-Cell; D012694:Serine; D011493:Protein Kinase C