The T Cell Receptor/CD3 Complex: A Dynamic Protein Ensemble

Clevers, Hans; Alarcón, Balbino; Wileman, Thomas; Terhorst, Cox

doi:10.1146/annurev.iy.06.040188.003213

Cited by 730 publications

(250 citation statements)

References 56 publications

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“…TCR is a disulfide heterodimer (α β or γ δ) intimately associated with at least five non-polymorphic polypeptide components of the CD3 molecule (γ, δ, ε, ζ and η) at the cell surface (Clevers et al, 1988;. The TCR/CD3 complex is assembled in the ER of T cells after synthesis of individual chains, further modified in the Golgi apparatus and transported to the cell surface (Carson et al, 1991).…”

Section: Introductionmentioning

confidence: 99%

Endoplasmic reticulum retention and degradation of T cell antigen receptor β chain

Lee

1998

Exp Mol Med

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The T cell antigen receptor-CD3 (TCR/CD3) complex is assembled in the endoplasmic reticulum (ER) of T cells after synthesis of individual chains, and is transported to the cell surface for immune recognition and regulation. Partially assembled or unassembled TCR chains are retained and rapidly degraded in the ER. These processes are strictly regulated in the ER at post-translational level for the maintenance of cellular homeostasis. In order to identify the region responsible for the ER retention and rapid degradation of the TCR chain, number of mutants were engineered and their fates, after synthesis in the ER of the HeLa cells, were investigated. Extensive mutagenic analysis of TCR chain, including changing the charged amino acid residues and two tyrosine residues of the transmembrane region into hydrophobic amino acid residues, did not alter the ER retention and rapid degradation. Soluble TCR chain and cytoplasmic tail truncation mutant were also rapidly degraded in the ER. However, N-glycosylation rate of soluble TCR chain in the ER was significantly increased possibily due to the increased exposure of the N-glycosylation site. These results suggest that the ER retention of TCR chain is mediated through its extracellular and transmembrane-cytoplasmic regions and that the rapid ER degradation can be caused by an exposure of unassembled subregion of TCR chain, either extracellular domain or hydrophobic transmembrane region to the hydrophilic environment (lumen of the ER) rather than by presence of a specific degradation signal.

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Section: Introductionmentioning

confidence: 99%

Endoplasmic reticulum retention and degradation of T cell antigen receptor β chain

Lee

1998

Exp Mol Med

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“…The TCR is a complex, multisubunit structure that consists of at least six chains (a and p, or y and 8, as well as the CD3 y, 8, e and C, chains) that are assembled in the endoplasmic reticulum and transported to the cell surface (reviewed in [1][2][3][4][5]. Whereas the a, p, y and 8 chains of the TCR are clonotypic and confer ligand specificity, the CD3 subunits are invariant and function as signal transducing molecules through interactions of their cytoplasmic domains with the protein tyrosine kinases ZAP-70 or pse' 0 * (6)(7)(8) Efficient surface expression of a functional TCR-CD3 complex on mature T cells has been shown to require all six chains (9).…”

Section: Introductionmentioning

confidence: 99%

Expression of genes encoding the pre-TCR and CD3 complex during thymus development

MacDonald

Malissen

1995

International Immunology

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The mature TCR is composed of a clonotypic heterodimer (ap" or 76) associated with the Invariant CD3 components (y, 8, e and Q. There is now considerable evidence that more immature forms of the TCR-CD3 complex (consisting of either CD3 alone or CD3 associated with a heterodimer of TCR p and pre-Ta) can be expressed at the cell surface on early thymocytes. These pre-TCR complexes are believed to be necessary for the ordered progression of early T cell development. We have analyzed in detail the expression of both the pre-TCR and CD3 complex at various stages of adult thymus development. Our data indicate that all CD3 components are already expressed at the mRNA level by the earliest identifiable (CD4 to ) thymic precursor. In contrast, genes encoding the pre-TCR complex (pre-Ta and fully rearranged TCR fJ) are first expressed at the CD44'°CD25 + CD4~CD8~ stage. Detectable surface expression of both CD3 and TCR f) are delayed relative to expression of the corresponding genes, suggesting the existence of other (as yet unidentified) components of the pre-TCR complex.

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“…Ionomycin enhances both the release of Ca 2÷ from intracellular stores and the influx of Ca 2÷ from the extracellular environment (Clevers et al, 1988;Gardner, 1989;Gelfand et al, 1987). Thus a pathway that enhances the free Ca 2÷ concentration within the cell may create conditions unfavourable for virus expression.…”

Section: Introductionmentioning

confidence: 99%

Calcium-mediated inhibition of phorbol ester and Tax trans-activation of the human T cell leukaemia virus type 1

Copeland

Haaksma

Goudsmit

et al. 1994

Journal of General Virology

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Human Jurkat T cells containing a stably integrated human T cell leukaemia virus type 1 (HTLV-1) long terminal repeat (LTR) reporter gene construct were used to study the role of calcium-dependent cellular activation pathways in LTR trans-activation. Treatment of these cells with the calcium ionophore ionomycin resulted in a reduced basal response of the LTR and reduced responses to 12-O-tetradecanoylphorbol-13-acetate-and Tax-mediated trans-activation. This effect was also observed for virus production in the HTLV-1-producing T cell line MT-2. Experiments designed to determine the events underlying this inhibition, using inhibitors of calcium-related events, revealed that the ionomycininduced repression of the LTR was alleviated in all cases by cyclosporin A. This compound was also effective in preventing the ionomycin-induced reduction in virus production in MT-2 cells. These results suggest a role for calcium-related events in the down-regulation of HTLV-1 expression.

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The T Cell Receptor/CD3 Complex: A Dynamic Protein Ensemble

Cited by 730 publications

References 56 publications

Endoplasmic reticulum retention and degradation of T cell antigen receptor β chain

Endoplasmic reticulum retention and degradation of T cell antigen receptor β chain

Expression of genes encoding the pre-TCR and CD3 complex during thymus development

Calcium-mediated inhibition of phorbol ester and Tax trans-activation of the human T cell leukaemia virus type 1

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