The CD3 gamma leucine-based receptor-sorting motif is required for efficient ligand-mediated TCR down-regulation

TY - JOUR

T1 - The CD3 gamma leucine-based receptor-sorting motif is required for efficient ligand-mediated TCR down-regulation

AU - von Essen, Marina

AU - Menné, Charlotte

AU - Nielsen, Bodil L

AU - Lauritsen, Jens Peter H

AU - Dietrich, Jes

AU - Andersen, Peter S

AU - Karjalainen, Klaus

AU - Ødum, Niels

AU - Geisler, Carsten

N1 - Keywords: Amino Acid Motifs; Amino Acid Sequence; Animals; Antigens, CD3; Cell Line; Cells, Cultured; Down-Regulation; Gene Deletion; Humans; Jurkat Cells; Kinetics; Leucine; Ligands; Mice; Molecular Sequence Data; Protein Kinase C; Receptor-CD3 Complex, Antigen, T-Cell; Sequence Homology; T-Lymphocytes

PY - 2002

Y1 - 2002

N2 - 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.

AB - 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.

M3 - Journal article

C2 - 11970997

SN - 0022-1767

VL - 168

SP - 4519

EP - 4523

JO - Journal of Immunology

JF - Journal of Immunology

IS - 9

ER -