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Constitutive and Ligand-Induced TCR Degradation ¹

Marina von Essen^*, Charlotte Menné Bonefeld^*, Volkert Siersma, Anette Bødker Rasmussen^*, Jens Peter H. Lauritsen^*, Bodil L. Nielsen^* and Carsten Geisler^2,*

^* Institute of Medical Microbiology and Immunology and Institute of Public Health, Department of Biostatistics, The Panum Institute, University of Copenhagen, Copenhagen, Denmark

Modulation of TCR expression levels is a central event during T cell development and activation, and it probably plays an important role in adjusting T cell responsiveness. Conflicting data have been published on down-regulation and degradation rates of the individual TCR subunits, and several divergent models for TCR down-regulation and degradation have been suggested. The aims of this study were to determine the rate constants for constitutive and ligand-induced TCR degradation and to determine whether the TCR subunits segregate or are processed as an intact unit during TCR down-regulation and degradation. We found that the TCR subunits in nonstimulated Jurkat cells were degraded with rate constants of 0.0011 min^–1, resulting in a half-life of 10.5 h. Triggering of the TCR by anti-TCR Abs resulted in a 3-fold increase in the degradation rate constants to 0.0033 min^–1, resulting in a half-life of 3.5 h. The subunits of the TCR complex were down-regulated from the cell surface and degraded with identical kinetics, and most likely remained associated during the passage throughout the endocytic pathway from the cell surface to the lysosomes. Similar results were obtained in studies of primary human V8⁺ T cells stimulated with superantigen. Based on these results, the simplest model for TCR internalization, sorting, and degradation is proposed.

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