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Agonist-induced T cell receptor down-regulation: molecular requirements and dissociation from T cell activation
Authors:Mariolina Salio  Salvatore Valitutti  Antonio Lanzavecchia
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-γ 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.
Keywords:T lymphocyte  T cell receptor down-regulation  Protein tyrosine kinase inhibitor
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