TY - JOUR
T1 - Constitutive and ligand-induced TCR degradation
AU - von Essen, Marina
AU - Bonefeld, Charlotte Menné
AU - Siersma, Volkert
AU - Rasmussen, Anette Bødker
AU - Lauritsen, Jens Peter H
AU - Nielsen, Bodil L
AU - Geisler, Carsten
N1 - Keywords: Antigens, CD3; Biotinylation; Dimerization; Endocytosis; Humans; Jurkat Cells; Ligands; Protein Subunits; Receptors, Antigen, T-Cell; T-Lymphocytes
PY - 2004
Y1 - 2004
N2 - 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.
AB - 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.
M3 - Journal article
C2 - 15210797
SN - 0022-1767
VL - 173
SP - 384
EP - 393
JO - Journal of Immunology
JF - Journal of Immunology
IS - 1
ER -