Two distinct pathways exist for down-regulation of the TCR
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TCR down-regulation plays an important role in modulating T cell responses both during T cell development and in mature T cells. Down-regulation of the TCR is induced by engagement of the TCR by specific ligands and/or by activation of protein kinase C (PKC). We report here that ligand- and PKC-induced TCR down-regulation is mediated by two distinct, independent mechanisms. Ligand-induced TCR down-regulation is dependent on the protein tyrosine kinases p56(lck) and p59(fyn) but independent of PKC and the CD3gamma leucine-based (L-based) internalization motif. In contrast, PKC-induced TCR down-regulation is dependent on the CD3gamma L-based internalization motif but independent of p56(lck) and p59(fyn). Finally, our data indicate that in the absence of TCR ligation, TCR expression levels can be finely regulated via the CD3gamma L-based motif by the balance between PKC and serine/threonine protein phosphatase activities. Such a TCR ligation-independent regulation of TCR expression levels could probably be important in determining the activation threshold of T cells in their encounter with APC.
|Journal||Journal of Immunology|
|Number of pages||7|
|Publication status||Published - 1998|
Keywords: Amino Acid Sequence; Down-Regulation; Humans; Jurkat Cells; Ligands; Molecular Sequence Data; Phosphoprotein Phosphatases; Phosphorylation; Protein Kinase C; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-fyn; Receptor-CD3 Complex, Antigen, T-Cell; Receptors, Antigen, T-Cell; T-Lymphocytes; Tyrosine; src-Family Kinases