On the Role of CD3δ Chains in TCRγδ/CD3 Complexes during Assembly and Membrane Expression

Alibaud, Laeticia; Arnaud, Jacques; Llobera, Régine; Rubin, Bent

doi:10.1046/j.1365-3083.2001.00938.x

Cited by 15 publications

(20 citation statements)

References 50 publications

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“…We propose that fugu B7-H1/DC is an orthologue of both the mammalian B7-H1 and B7-DC. The mammalian B7-H1 and B7-DC genes might have emerged in a similar manner to that of mammalian CD3 genes (27).…”

Section: Discussionmentioning

confidence: 97%

Teleost B7 Expressed on Monocytes Regulates T Cell Responses

Sugamata

Suetake

Kikuchi

et al. 2009

The Journal of Immunology

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In mammals, professional APCs induce adaptive immunity via the activation of T cells. During this process, B7 family molecules present upon APCs are known to play crucial roles in optimal T cell stimulation. In contrast, the confirmation of APCs in a nonmammalian vertebrate has yet to be achieved. To obtain further insights into the evolutionary origin of APCs, we have identified three members of the B7 family in the teleost Takifugu rubripes (fugu): B7-H1/DC, B7-H3, and B7-H4. The three fugu B7s were expressed on the surface of blood monocytes. The B7 ؉ monocytes, which are composed of at least two distinct populations, expressed the MHC class II component gene. The fugu B7 molecules bound to activated T cells, indicating that putative B7 receptors were expressed upon T cells. Fugu B7-H1/DC inhibited T cell proliferation concomitant with increasing levels of both IL-10 and IFN-␥ expression, whereas both B7-H3 and B7-H4 promoted T cell growth following IL-2 induction and the suppression of IL-10. These observations indicate that fugu B7s regulate T cell responses via receptors upon T cells. We suggest that fish B7 ؉ monocytes are APCs and that a costimulatory system has already developed in fish via the evolutionary process.

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Section: Discussionmentioning

confidence: 97%

Teleost B7 Expressed on Monocytes Regulates T Cell Responses

Sugamata

Suetake

Kikuchi

et al. 2009

The Journal of Immunology

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“…The issue of TCR stoichiometry is important to resolve in order to understand how the TCR manages the diverse signaling pathways under its supervision. In contrast to αβ TCRs, γδ TCRs are assembled with much less CD3 δ in the complex, which may have effects on γδ TCR signaling (43, 44). In fact, γδ TCRs are expressed well in CD3 δ‐deficient mice, while αβ TCRs are not (45).…”

Section: Surface Expression Subunit Composition and Stoichiometry Omentioning

confidence: 99%

Surface T‐cell antigen receptor expression and availability for long‐term antigenic signaling

Schrum

Turka

Palmer

2003

Immunological Reviews

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It is important to understand how T-cell antigen receptor (TCR) engagement and signaling are regulated throughout an immune response. This review examines the dynamics of surface TCR expression and signaling capacity during thymic and effector T-cell development. Although the TCR can undergo vast changes in surface expression, T cells remain capable of sustaining TCR engagement for long periods of time. This may be achieved by a combination of mechanisms that involve (a) controlling the quantity of surface TCR available for ligand interaction and (b) controlling the quality of surface TCR expression during T-cell activation. TCR signaling itself appears to be one of the main quantitative modulators of surface TCR expression, and it can cause both downregulation and upregulation at different times of T-cell activation. Recent studies indicate that the degree of upregulation is tunable by the strength of antigenic stimulation. There is evidence that qualitatively distinct forms of the TCR exist, and their potential role in sustained antigenic signaling is also discussed. A goal of future studies will be to better characterize these modulations in surface TCR expression and to clarify their impact on the regulation of immune responses.

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“…This may favour the incorporation of competing CD3δε dimers to nascent γδ TCR complexes (step 2), and would ultimately lead to γδ TCR receptors devoid of the required stability for optimal surface expression. Moreover, human TCRδ (but not TCRα) can stably recruit not only CD3δε but also CD3γε [14] during step1, which may reduce further the availability of CD3γε dimers for step2 when CD3γ is limiting (not shown).…”

Section: Discussionmentioning

confidence: 99%

Human CD3γ, but not CD3δ, haploinsufficiency differentially impairs γδ versus αβ surface TCR expression

et al. 2013

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BackgroundThe T cell antigen receptors (TCR) of αβ and γδ T lymphocytes are believed to assemble in a similar fashion in humans. Firstly, αβ or γδ TCR chains incorporate a CD3δε dimer, then a CD3γε dimer and finally a ζζ homodimer, resulting in TCR complexes with the same CD3 dimer stoichiometry. Partial reduction in the expression of the highly homologous CD3γ and CD3δ proteins would thus be expected to have a similar impact in the assembly and surface expression of both TCR isotypes. To test this hypothesis, we compared the surface TCR expression of primary αβ and γδ T cells from healthy donors carrying a single null or leaky mutation in CD3G (γ+/−) or CD3D (δ+/−, δ+/leaky) with that of normal controls.ResultsAlthough the partial reduction in the intracellular availability of CD3γ or CD3δ proteins was comparable as a consequence of the mutations, surface TCR expression measured with anti-CD3ε antibodies was significantly more decreased in γδ than in αβ T lymphocytes in CD3γ+/− individuals, whereas CD3δ+/− and CD3δ+/leaky donors showed a similar decrease of surface TCR in both T cell lineages. Therefore, surface γδ TCR expression was more dependent on available CD3γ than surface αβ TCR expression.ConclusionsThe results support the existence of differential structural constraints in the two human TCR isotypes regarding the incorporation of CD3γε and CD3δε dimers, as revealed by their discordant surface expression behaviour when confronted with reduced amounts of CD3γ, but not of the homologous CD3δ chain. A modified version of the prevailing TCR assembly model is proposed to accommodate these new data.

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On the Role of CD3δ Chains in TCRγδ/CD3 Complexes during Assembly and Membrane Expression

Cited by 15 publications

References 50 publications

Teleost B7 Expressed on Monocytes Regulates T Cell Responses

Teleost B7 Expressed on Monocytes Regulates T Cell Responses

Surface T‐cell antigen receptor expression and availability for long‐term antigenic signaling

Human CD3γ, but not CD3δ, haploinsufficiency differentially impairs γδ versus αβ surface TCR expression

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