Structure of the T cell receptor in a TiαVβ2,αVβ8‐positive T cell line

Hou, Xiaohong; Dietrich, Jes; Kuhlmann, Jan Dominik; Wegener, Anne-Marie K.; Geisler, Carsten

doi:10.1002/eji.1830240534

Cited by 19 publications

(22 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The TCR comprises the clonotypic Ti § g heterodimer, the CD3 + 4 and CD3ˇ4 heterodimers, and the TCR´2 homodimer [1][2][3][4][5]. The Ti § g heterodimer is responsible for recognition of antigen [6,7] and the associated CD3 and TCR´chains are responsible for the signaling events that follow antigen recognition [8].…”

Section: Introductionmentioning

confidence: 99%

TCRζ is transported to and retained in the Golgi apparatus independently of other TCR chains: implications for TCR assembly

et al. 1999

Self Cite

View full text Add to dashboard Cite

It is generally assumed that TCR assembly occurs in the endoplasmic reticulum (ER), and ER retention/degradation signals have been identified in several of the TCR chains. These signals are probably responsible for retention of incompletely assembled TCR complexes and free TCR chains in the ER. This study focused on the intracellular localization and transport of partially assembled TCR complexes as determined by confocal microscopy analyses. We found that none of the TCR chains except for TCR´were allowed to exit the ER in T cell variants in which the hexameric CD3 + 4 Ti § g CD3ˇ4 complex was not formed. Interestingly, TCRẃ as exported from the ER independently of other TCR chains and was predominantly located in a compartment identified as the Golgi apparatus. Furthermore, in the TCR´-negative cell line MA5.8, the hexameric CD3 + 4 Ti § g CD3ˇ4 complex was allowed to exit the ER and was also predominantly located in the Golgi apparatus. However, neither hexameric TCR complexes nor TCR´chains were efficiently expressed at the cell surface without the other. The observations that TCR´and hexameric TCR complexes are transported from the ER to the Golgi apparatus independently of each other and that these partial TCR complexes are unable to be efficiently expressed at the cell surface suggest that final TCR assembly occurs in the Golgi apparatus.

show abstract

Section: Introductionmentioning

confidence: 99%

TCRζ is transported to and retained in the Golgi apparatus independently of other TCR chains: implications for TCR assembly

et al. 1999

Self Cite

View full text Add to dashboard Cite

show abstract

“…The TCR is a multisubunit complex composed of at least eight subunits organized in four dimers: Ti␣␤, CD3␥⑀, CD3␦⑀, and dimers (1)(2)(3)(4). The ␣-and ␤-chains of the Ti␣␤ dimer are covalently linked by a disulfide bridge as are the -chains of the homodimer, whereas the chains of the CD3 dimers are noncovalently linked.…”

mentioning

confidence: 99%

Constitutive and Ligand-Induced TCR Degradation

Essen

Bonefeld

Siersma

et al. 2004

The Journal of Immunology

Self Cite

View full text Add to dashboard Cite

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 Vβ8+ T cells stimulated with superantigen. Based on these results, the simplest model for TCR internalization, sorting, and degradation is proposed.

show abstract

“…T he TCR comprises the clonotypic Ti␣ and ␤ chains and the invariant CD3␥, ⑀, ␦, and chains (1)(2)(3)(4)(5)(6). The ␣-and ␤-chains are responsible for the specific recognition of peptide-MHC complexes and the signaling events following Ag recognition are mediated by the CD3 and -chains (7)(8)(9).…”

mentioning

confidence: 99%

TCR Comodulation of Nonengaged TCR Takes Place by a Protein Kinase C and CD3γ Di-Leucine-Based Motif-Dependent Mechanism

Bonefeld

Rasmussen

Lauritsen

et al. 2003

The Journal of Immunology

Self Cite

View full text Add to dashboard Cite

One of the earliest events following TCR triggering is TCR down-regulation. However, the mechanisms behind TCR down-regulation are still not fully known. Some studies have suggested that only directly triggered TCR are internalized, whereas others studies have indicated that, in addition to triggered receptors, nonengaged TCR are also internalized (comodulated). In this study, we used transfected T cells expressing two different TCR to analyze whether comodulation took place. We show that TCR triggering by anti-TCR mAb and peptide-MHC complexes clearly induced internalization of nonengaged TCR. By using a panel of mAb against the Tiβ chain, we demonstrate that the comodulation kinetics depended on the affinity of the ligand. Thus, high-affinity mAb (KD = 2.3 nM) induced a rapid but reversible comodulation, whereas low-affinity mAb (KD = 6200 nM) induced a slower but more permanent type of comodulation. Like internalization of engaged TCR, comodulation was dependent on protein tyrosine kinase activity. Finally, we found that in contrast to internalization of engaged TCR, comodulation was highly dependent on protein kinase C activity and the CD3γ di-leucine-based motif. Based on these observations, a physiological role of comodulation is proposed and the plausibility of the TCR serial triggering model is discussed.

show abstract

Structure of the T cell receptor in a TiαVβ2,αVβ8‐positive T cell line

Cited by 19 publications

References 31 publications

TCRζ is transported to and retained in the Golgi apparatus independently of other TCR chains: implications for TCR assembly

TCRζ is transported to and retained in the Golgi apparatus independently of other TCR chains: implications for TCR assembly

Constitutive and Ligand-Induced TCR Degradation

TCR Comodulation of Nonengaged TCR Takes Place by a Protein Kinase C and CD3γ Di-Leucine-Based Motif-Dependent Mechanism

Contact Info

Product

Resources

About