HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Dietrich, J. Articles by Geisler, C. Search for Related Content PubMed PubMed Citation Articles by Dietrich, J. Articles by Geisler, C. Pubmed/NCBI databases Substance via MeSH

Ligand-Induced TCR Down-Regulation Is Not Dependent on Constitutive TCR Cycling¹

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

TCR internalization takes place both in resting T cells as part of constitutive TCR cycling, after PKC activation, and during TCR triggering. It is still a matter of debate whether these pathways represent distinct pathways. Thus, some studies have indicated that ligand-induced TCR internalization is regulated by mechanisms distinct from those involved in constitutive internalization, whereas other studies have suggested that the ligand-induced TCR internalization pathway is identical with the constitutive pathway. To resolve this question, we first identified requirements for constitutive TCR cycling. We found that in contrast to PKC-induced TCR internalization where both CD3-S¹²⁶ and the CD3 leucine-based internalization motif are required, constitutive TCR cycling required neither PKC nor CD3-S¹²⁶ but only the CD3 leucine-based motif. Having identified these requirements, we next studied ligand-induced internalization in cells with abolished constitutive TCR cycling. We found that ligand-induced TCR internalization was not dependent on constitutive TCR internalization. Likewise, constitutive internalization and recycling of the TCR were independent of an intact ligand-induced internalization of the TCR. In conclusion, ligand-induced TCR internalization and constitutive cycling of the TCR represents two independent pathways regulated by different mechanisms.

This article has been cited by other articles:

				C. M. Bonefeld, M. Haks, B. Nielsen, M. von Essen, L. Boding, A. K. Hansen, J. M. Larsen, N. Odum, P. Krimpenfort, A. Kruisbeek, et al. TCR Down-Regulation Controls Virus-Specific CD8+ T Cell Responses J. Immunol., December 1, 2008; 181(11): 7786 - 7799. [Abstract] [Full Text] [PDF]

				D. A. Alvarez-Arias and K. S. Campbell Protein Kinase C Regulates Expression and Function of Inhibitory Killer Cell Ig-Like Receptors in NK Cells J. Immunol., October 15, 2007; 179(8): 5281 - 5290. [Abstract] [Full Text] [PDF]

				S. Davanture, J. Leignadier, P. Milani, P. Soubeyran, B. Malissen, M. Malissen, A.-M. Schmitt-Verhulst, and C. Boyer Selective Defect in Antigen-Induced TCR Internalization at the Immune Synapse of CD8 T Cells Bearing the ZAP-70(Y292F) Mutation J. Immunol., September 1, 2005; 175(5): 3140 - 3149. [Abstract] [Full Text] [PDF]

				B. M. Badran, K. Kunstman, J. Stanton, M. Moschitta, A. Zerghe, H. Akl, A. Burny, S. M. Wolinsky, and K. E. Willard-Gallo Transcriptional Regulation of the Human CD3{gamma} Gene: The TATA-Less CD3{gamma} Promoter Functions via an Initiator and Contiguous Sp-Binding Elements J. Immunol., May 15, 2005; 174(10): 6238 - 6249. [Abstract] [Full Text] [PDF]

				V Yadav, G Marracci, J Lovera, W Woodward, K Bogardus, W Marquardt, L Shinto, C Morris, and D Bourdette Lipoic acid in multiple sclerosis: a pilot study Multiple Sclerosis, April 1, 2005; 11(2): 159 - 165. [Abstract] [PDF]

				A. L. Szymczak and D. A. A. Vignali Plasticity and Rigidity in Adaptor Protein-2-Mediated Internalization of the TCR:CD3 Complex J. Immunol., April 1, 2005; 174(7): 4153 - 4160. [Abstract] [Full Text] [PDF]

				A. Monjas, A. Alcover, and B. Alarcon Engaged and Bystander T Cell Receptors Are Down-modulated by Different Endocytotic Pathways J. Biol. Chem., December 31, 2004; 279(53): 55376 - 55384. [Abstract] [Full Text] [PDF]

				C. M. Bonefeld, A. B. Rasmussen, J. P. H. Lauritsen, M. von Essen, N. Odum, P. S. Andersen, and C. Geisler TCR Comodulation of Nonengaged TCR Takes Place by a Protein Kinase C and CD3{gamma} Di-Leucine-Based Motif-Dependent Mechanism J. Immunol., September 15, 2003; 171(6): 3003 - 3009. [Abstract] [Full Text] [PDF]

				P. S. Torres, A. Alcover, D. A. Zapata, J. Arnaud, A. Pacheco, J. M. Martin-Fernandez, E. M. Villasevil, O. Sanal, and J. R. Regueiro TCR Dynamics in Human Mature T Lymphocytes Lacking CD3{gamma} J. Immunol., June 15, 2003; 170(12): 5947 - 5955. [Abstract] [Full Text] [PDF]

				F. Borrego, J. Kabat, T. B. Sanni, and J. E. Coligan NK Cell CD94/NKG2A Inhibitory Receptors Are Internalized and Recycle Independently of Inhibitory Signaling Processes J. Immunol., December 1, 2002; 169(11): 6102 - 6111. [Abstract] [Full Text] [PDF]