title: The CD3 gamma leucine-based receptor-sorting motif is required for efficient ligand-mediated TCR down-regulation.
abstract: TCR down-regulation plays an important role in modulating T cell responses both during T cell development and in mature T cells. At least two distinct pathways exist for down-regulation of the TCR. One pathway is activated following TCR ligation and is dependent on tyrosine phosphorylation. The other pathway is dependent on protein kinase C (PKC)-mediated activation of the CD3 gamma di-leucine-based receptor-sorting motif. Previous studies have failed to demonstrate a connection between ligand- and PKC-induced TCR down-regulation. Thus, although an apparent paradox, the dogma has been that ligand- and PKC-induced TCR down-regulations are not interrelated. By analyses of a newly developed CD3 gamma-negative T cell variant, freshly isolated and PHA-activated PBMC, and a mouse T cell line, we challenged this dogma and demonstrate in this work that PKC activation and the CD3 gamma di-leucine-based motif are indeed required for efficient ligand-induced TCR down-regulation.
authors.affiliation: Institute of Medical Microbiology and Immunology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Marina
authors.initials: M
authors.lastname: von Essen
authors.forename: Charlotte
authors.initials: C
authors.lastname: Menné
authors.forename: Bodil L
authors.initials: BL
authors.lastname: Nielsen
authors.forename: Jens Peter H
authors.initials: JP
authors.lastname: Lauritsen
authors.forename: Jes
authors.initials: J
authors.lastname: Dietrich
authors.forename: Peter S
authors.initials: PS
authors.lastname: Andersen
authors.forename: Klaus
authors.initials: K
authors.lastname: Karjalainen
authors.forename: Niels
authors.initials: N
authors.lastname: Ødum
authors.forename: Carsten
authors.initials: C
authors.lastname: Geisler
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D017252:CD3 Complex / Q000737:chemistry* / Q000235:genetics; D002460:Cell Line; D002478:Cells, Cultured; D015536:Down-Regulation; D017353:Gene Deletion; D006801:Humans; D019169:Jurkat Cells; D007700:Kinetics; D007930:Leucine / Q000737:chemistry*; D008024:Ligands; D051379:Mice; D008969:Molecular Sequence Data; D011493:Protein Kinase C / Q000502:physiology; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000378:metabolism*; D017385:Sequence Homology; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D017252:CD3 Complex; C452842:CD3 antigen, gamma chain; D008024:Ligands; D017260:Receptor-CD3 Complex, Antigen, T-Cell; D011493:Protein Kinase C; D007930:Leucine