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The Journal of Immunology, 2002, 168: 4519-4523.
Copyright © 2002 by The American Association of Immunologists

The CD3{gamma} Leucine-Based Receptor-Sorting Motif Is Required for Efficient Ligand-Mediated TCR Down-Regulation1

Marina von Essen, Charlotte Menné, Bodil L. Nielsen, Jens Peter H. Lauritsen, Jes Dietrich, Peter S. Andersen, Klaus Karjalainen, Niels Ødum and Carsten Geisler2

Institute of Medical Microbiology and Immunology, University of Copenhagen, Copenhagen, Denmark

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.




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