The mouse vitronectin receptor is a T cell activation antigen.

Moulder, Kevin; Roberts, Kevan; Shevach, Ethan M.; Coligan, J E

doi:10.1084/jem.173.2.343

Cited by 47 publications

(29 citation statements)

References 28 publications

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“…Moreover, integrin a v b 3 expression is upregulated on activated T cells [32], suggesting that integrin a v b 3 positively regulates immune responses at the interface between DC and T cells. Our present data showed that gp49B À/À DC can induce the proliferation of CD4 1 T cells better than that of CD8 1 T cells.…”

Section: Discussionmentioning

confidence: 99%

“…In contrast, gp49B contains two ITIM in its cytoplasmic portion, and inhibits activation signals upon cellular engagement with other activating receptors by recruiting SHP-1 to phosphotyrosylated ITIM [27,29]. gp49B binds to integrin a v and b 3 chains (a v b 3 ), which are expressed on a variety of cells including platelets, lymphocytes, and endothelial cells [30][31][32][33]. Colligation of gp49B with the highaffinity receptor for IgE or the type I FcgR by antibodies inhibits degranulation of mast cells or production of TNF-a by macrophages, respectively [29,34].…”

Section: Introductionmentioning

confidence: 99%

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A novel regulatory role of gp49B on dendritic cells in T‐cell priming

et al. 2008

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Dendritic cells (DC) play pivotal roles in the induction and regulation of both innate and acquired immunity. DC express several cell-surface immune inhibitory receptors. However, little is known about their potential immunoregulatory functions in the context of T-cell activation. Here we report that murine gp49B, a member of the immunoglobulin superfamily, harboring immunoreceptor tyrosine-based inhibitory motifs, is expressed on DC and downregulates cellular activity to prevent the excessive activation of T cells in vitro and in vivo. Bone marrow-derived DC (BMDC) from newly generated gp49B-deficient (gp49B À/À ) mice induced enhanced proliferation and IL-2 release of antigen-specific CD4 1 and CD8 1 T cells compared with BMDC from wild-type mice, in a cell-cell contact manner. The enhanced proliferation by gp49B À/À BMDC was also observed in allogeneic CD4 1 and CD8 1 T cells. Moreover, the transfer of allogeneic BALB/c splenocytes into C57BL/6 gp49B À/À mice induced severe acute graft-versus-host disease with an augmented upregulation of CD86 on CD11c 1 splenic gp49B À/À DC, while transfer of C57BL/6 gp49B À/À splenocytes into BALB/c mice did not, suggesting the exacerbation of the disease was due, at least in part, to augmented activation of recipient gp49B À/À DC. These findings demonstrate a novel regulatory role of gp49B in the function of DC.Key words: Antigen presentation Á Costimulation Á DC Á Regulatory receptor Á Tolerance IntroductionDendritic cells (DC) are professional antigen-presenting cells that recognize a diverse repertoire of antigens and present them to naïve T cells for the induction of acquired immunity [1]. DC are also related to innate immunity by producing cytokines such as both type I and II IFN, or by activating NK cells [2,3]. In addition, recent reports revealed that a subset of DC maintains peripheral tolerance in the steady state [4], showing that DC play a pivotal role in the induction of immune responses including autoimmunity.On the DC surface, a variety of structurally different immunoreceptors that regulate DC and T-cell functions have been found, including CD80, CD86, CD40, and various Ig superfamily and lectin family molecules [5]. Among them, a group of paired Ig superfamily receptors, termed Ig-like receptors, have been attracting the interest of many researchers because they are expressed on various subsets of DC and are considered to contribute to the development or activation of DC [6][7][8][9][10]. Generally, Ig-like receptors are subdivided into two types, namely activating and inhibitory receptors, and in some cases they are expressed on hematopoietic cells in a pair-wise manner [11][12][13][14]. Most activating receptors associate with homodimeric subunits containing ITAM, such as the FcR common g chain and KARAP/DAP12 [15,16], and deliver positive signals into the cells through interaction with their ligands [17]. For instance, the uptake of immune complexes through activating FcR for IgG 2426augments DC maturation, leading to efficient antigen presentation [18...

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A novel regulatory role of gp49B on dendritic cells in T‐cell priming

et al. 2008

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“…Several extracellular matrix proteins, including fibronectin, collagen, vitronectin, and laminin, have been shown to influence T cell functions by inducing T cell adhesion, motility, trafficking, and T cell coactivation (12)(13)(14). However, recent data using tenascin suggest that some matrix proteins can inhibit TCR-mediated T cell activation (15).…”

Section: Thrombospondin-1 Inhibits Tcr-mediated T Lymphocyte Early Acmentioning

confidence: 99%

Thrombospondin-1 Inhibits TCR-Mediated T Lymphocyte Early Activation

Wilson

et al. 2001

The Journal of Immunology

109

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Biological activities of the matrix glycoprotein thrombospondin-1 (TSP1) are cell type specific and depend on the relative expression or activation of several TSP1 receptors. Although engaging individual TSP1 receptors in T lymphocytes can elicit costimulating signals, in this study we show that intact TSP1 inhibits TCR-mediated T cell activation, assessed globally using cDNA microarrays. TSP1 signaling suppressed expression of several genes induced in Jurkat T cells, including the T cell activation markers CD69, early growth response gene-1 (Egr-1), and phosphatase of activated cells (PAC-1). TCR-stimulated and CD47-costimulated IL-2 secretion and cell surface CD69 expression were also inhibited by TSP1. The specific inhibitory effect of TSP1 was verified in freshly isolated human PBMCs. TSP1 inhibited TCR-mediated but not protein kinase C-mediated T cell activation. Using CD69 expression as a marker, we demonstrated that the inhibitory activity of TSP1 depended on two TSP1 receptors, CD47 and integrin-associated protein heparan sulfate proteoglycans. Signals from these receptors inhibited TCR signaling downstream of ZAP70, but upstream of NF-AT. Therefore, the expression of TSP1 induced during wound repair and in tumor stroma may limit T cell activation at these sites.

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“…Although gp49A has a short cytoplasmic tail that lacks any specific signaling motifs, gp49B contains two ITIMs in its cytoplasmic tail that mediate inhibition of cellular activation by recruiting SHP-1 and SHP-2 (26)(27)(28)(29). gp49B has been shown to bind to the integrin a v and b 3 (a v b 3 ), which is expressed on a variety of cells including activated T cells, and this interaction inhibits IgE-dependent degranulation of mast cells (30)(31)(32). Other studies showed that gp49B is also expressed on activated T cells and NK cells, and regulates IFN-g production (32)(33)(34).…”

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confidence: 99%

gp49B-Mediated Negative Regulation of Antibody Production by Memory and Marginal Zone B Cells

Fukao

Haniuda

Nojima

et al. 2014

The Journal of Immunology

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The rapid Ab responses observed after primary and secondary immunizations are mainly derived from marginal zone (MZ) and memory B cells, respectively, but it is largely unknown how these responses are negatively regulated. Several inhibitory receptors have been identified and their roles have been studied, but mainly on follicular B cells and much less so on MZ B, and never on memory B cells. gp49B is an Ig superfamily member that contains two ITIMs in its cytoplasmic tail, and it has been shown to negatively regulate mast cell, macrophage, and NK cell responses. In this study, we demonstrate that gp49B is preferentially expressed on memory and MZ B cells. We show that gp49B−/− mice produce more IgM after a primary immunization and more IgM and IgG1 after a secondary immunization than gp49B+/+ mice in T cell–dependent immune responses. Memory and MZ B cells from gp49B−/− mice also produce more Abs upon in vitro stimulation with CD40 than those from gp49B+/+ mice. The in vitro IgM production by MZ B cells from gp49B+/+, but not gp49B−/−, mice is suppressed by interaction with a putative gp49B ligand, the integrin αvβ3 heterodimer. In addition, gp49B−/− mice exhibited exaggerated IgE production in the memory recall response. These results suggest that plasma cell development from memory and MZ B cells, as well as subsequent Ab production, are suppressed via gp49B. In memory B cells, this suppression also prevents excessive IgE production, thus curtailing allergic diseases.

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The mouse vitronectin receptor is a T cell activation antigen.

Cited by 47 publications

References 28 publications

A novel regulatory role of gp49B on dendritic cells in T‐cell priming

A novel regulatory role of gp49B on dendritic cells in T‐cell priming

Thrombospondin-1 Inhibits TCR-Mediated T Lymphocyte Early Activation

gp49B-Mediated Negative Regulation of Antibody Production by Memory and Marginal Zone B Cells

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