title: Agonist-induced T cell receptor down-regulation: molecular requirements and dissociation from T cell activation.
abstract: T cell receptor (TCR) down-regulation is a consequence of specific receptor engagement and plays an important role in modulating the T cell response. We have investigated the role of protein kinase C (PKC) and protein tyrosine kinases (PTK) in the induction of TCR down-regulation. We report that the mutation of S126 in the CD3-gamma chain that is known to inhibit phorbol-12-myristate 13-acetate-induced TCR down-regulation does not affect down-regulation induced by a specific agonist. In addition, agonist-induced TCR down-regulation is not affected by blockade or depletion of PKC, neither by blockade or lack of PTK, while the same treatments efficiently interfere with T cell activation. These results demonstrate that TCR down-regulation is induced by early events which follow specific engagement by an agonist and can be dissociated from those required for full T cell activation.
authors.affiliation: Basel Institute for Immunology, Switzerland. salio@bii.ch
authors.forename: M
authors.initials: M
authors.lastname: Salio
authors.forename: S
authors.initials: S
authors.lastname: Valitutti
authors.forename: A
authors.initials: A
authors.lastname: Lanzavecchia
mesh_terms: D017252:CD3 Complex / Q000502:physiology; D015536:Down-Regulation / Q000187:drug effects / Q000276:immunology*; D004789:Enzyme Activation / Q000187:drug effects / Q000276:immunology; D006801:Humans; D019169:Jurkat Cells; D008213:Lymphocyte Activation / Q000187:drug effects*; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011948:Receptors, Antigen, T-Cell / Q000819:agonists / Q000187:drug effects* / Q000378:metabolism*; D013601:T-Lymphocytes / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D019061:src-Family Kinases / Q000502:physiology
chemical_list: D017252:CD3 Complex; D011948:Receptors, Antigen, T-Cell; D011505:Protein-Tyrosine Kinases; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D019061:src-Family Kinases; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate