The CD3 gamma leucine-based receptor-sorting motif is required for efficient ligand-mediated TCR down-regulation.
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.
von Essen
Marina
M
Institute of Medical Microbiology and Immunology, University of Copenhagen, Copenhagen, Denmark.
Menné
Charlotte
C
Nielsen
Bodil L
BL
Lauritsen
Jens Peter H
JP
Dietrich
Jes
J
Andersen
Peter S
PS
Karjalainen
Klaus
K
Ødum
Niels
N
Geisler
Carsten
C
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*
D017252:CD3 Complex; C452842:CD3 antigen, gamma chain; D008024:Ligands; D017260:Receptor-CD3 Complex, Antigen, T-Cell; D011493:Protein Kinase C; D007930:Leucine