Constitutive and ligand-induced TCR degradation

Marina von Essen; Charlotte Menné Bonefeld; Volkert Siersma; Anette Bødker Rasmussen; Jens Peter H Lauritsen; Bodil L Nielsen; Carsten Geisler

Constitutive and ligand-induced TCR degradation

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

Ph.d.-studienævnet for Medicin

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

48 Citationer (Scopus)

Abstract

Udgivelsesdato: 2004-Jul-1

Originalsprog	Engelsk
Tidsskrift	Journal of Immunology
Vol/bind	173
Udgave nummer	1
Sider (fra-til)	384-93
Antal sider	9
ISSN	0022-1767
Status	Udgivet - 2004

Bibliografisk note

Keywords: Antigens, CD3; Biotinylation; Dimerization; Endocytosis; Humans; Jurkat Cells; Ligands; Protein Subunits; Receptors, Antigen, T-Cell; T-Lymphocytes

Citationsformater

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title = "Constitutive and ligand-induced TCR degradation",

abstract = "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.",

author = "{von Essen}, Marina and Bonefeld, {Charlotte Menn{\'e}} and Volkert Siersma and Rasmussen, {Anette B{\o}dker} and Lauritsen, {Jens Peter H} and Nielsen, {Bodil L} and Carsten Geisler",

note = "Keywords: Antigens, CD3; Biotinylation; Dimerization; Endocytosis; Humans; Jurkat Cells; Ligands; Protein Subunits; Receptors, Antigen, T-Cell; T-Lymphocytes",

year = "2004",

language = "English",

volume = "173",

pages = "384--93",

journal = "Journal of Immunology",

issn = "0022-1767",

publisher = "American Association of Immunologists",

number = "1",

}

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

VL - 173

SP - 384

EP - 393

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 1

ER -