Constitutive and ligand-induced TCR degradation.
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 approximately 0.0011 min(-1), resulting in a half-life of approximately 10.5 h. Triggering of the TCR by anti-TCR Abs resulted in a 3-fold increase in the degradation rate constants to approximately 0.0033 min(-1), resulting in a half-life of approximately 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 Vbeta8+ T cells stimulated with superantigen. Based on these results, the simplest model for TCR internalization, sorting, and degradation is proposed.
von Essen
Marina
M
Institute of Medical Microbiology and Immunology, Department of Biostatistics, The Panum Institute, Building 22.5, University of Copenhagen, Blegdamsvej 3C, DK-2200 Copenhagen, Denmark.
Bonefeld
Charlotte Menné
CM
Siersma
Volkert
V
Rasmussen
Anette Bødker
AB
Lauritsen
Jens Peter H
JP
Nielsen
Bodil L
BL
Geisler
Carsten
C
D019921:Biotinylation; D017252:CD3 Complex / Q000378:metabolism; D019281:Dimerization; D004705:Endocytosis; D006801:Humans; D019169:Jurkat Cells; D008024:Ligands; D021122:Protein Subunits; D011948:Receptors, Antigen, T-Cell / Q000737:chemistry / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism
D017252:CD3 Complex; C121704:CD3 antigen, zeta chain; D008024:Ligands; D021122:Protein Subunits; D011948:Receptors, Antigen, T-Cell