title: Two distinct pathways exist for down-regulation of the TCR.
abstract: 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.
authors.affiliation: Institute of Medical Microbiology and Immunology, University of Copenhagen, The Panum Institute, Denmark.
authors.forename: J P
authors.initials: JP
authors.lastname: Lauritsen
authors.forename: M D
authors.initials: MD
authors.lastname: Christensen
authors.forename: J
authors.initials: J
authors.lastname: Dietrich
authors.forename: J
authors.initials: J
authors.lastname: Kastrup
authors.forename: N
authors.initials: N
authors.lastname: Odum
authors.forename: C
authors.initials: C
authors.lastname: Geisler
mesh_terms: D000595:Amino Acid Sequence; D015536:Down-Regulation / Q000276:immunology*; D006801:Humans; D019169:Jurkat Cells; D008024:Ligands; D008969:Molecular Sequence Data; D010749:Phosphoprotein Phosphatases / Q000378:metabolism; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000502:physiology; D051076:Proto-Oncogene Proteins c-fyn; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000096:biosynthesis / Q000378:metabolism*; D013601:T-Lymphocytes / Q000201:enzymology / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism; D019061:src-Family Kinases / Q000502:physiology
chemical_list: D008024:Ligands; D011518:Proto-Oncogene Proteins; D017260:Receptor-CD3 Complex, Antigen, T-Cell; D011948:Receptors, Antigen, T-Cell; D014443:Tyrosine; C494957:FYN protein, human; D051076:Proto-Oncogene Proteins c-fyn; C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases; D011493:Protein Kinase C; D010749:Phosphoprotein Phosphatases