Microbial isoprenoid biosynthesis and human γδ T cell activation

Eberl, Matthias; Hintz, Martin; Reichenberg, Armin; Kollas, Ann-Kristin; Wiesner, Jochen; Jomaa, Hassan

doi:10.1016/s0014-5793(03)00483-6

Cited by 261 publications

(295 citation statements)

References 68 publications

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“…By far the most potent of these 'phosphoantigens' is (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMB-PP), an intermediate of the non-mevalonate pathway that is found in the majority of Gram-negative bacteria and many Gram-positive species as well as apicomplexan parasites such as Plasmodium falciparum and Toxoplasma gondii [11,15]. In these organisms, HMB-PP is converted into isopentenyl pyrophosphate (IPP) and dimethylallyl pyrophosphate (DMAPP), two further 'phosphoantigens' with a bioactivity approx.…”

Section: Innate-like Pattern Recognition By Human Vc9/vd2 T Cellsmentioning

confidence: 99%

“…Vc9/Vd2 T cells uniformly respond to a class of low molecular weight molecules often referred to as 'phosphoantigens' that represent metabolites of the isoprenoid biosynthesis, or synthetic analogs thereof. By far the most potent of these 'phosphoantigens' is (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMB-PP), an intermediate of the non-mevalonate pathway that is found in the majority of Gram-negative bacteria and many Gram-positive species as well as apicomplexan parasites such as Plasmodium falciparum and Toxoplasma gondii [11,15]. In these organisms, HMB-PP is converted into isopentenyl pyrophosphate (IPP) and dimethylallyl pyrophosphate (DMAPP), two further 'phosphoantigens' with a http://dx.doi.org/10.1016/j.cellimm.2015.01.008 0008-8749/Ó 2015 Published by Elsevier Inc.…”

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confidence: 99%

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Human Vγ9/Vδ2 T cells: Innate adaptors of the immune system

Tyler

Doherty

Moser

et al. 2015

Cellular Immunology

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a b s t r a c tUnconventional T cells are gaining center stage as important effector and regulatory cells that orchestrate innate and adaptive immune responses. Human Vc9/Vd2 T cells are amongst the best understood unconventional T cells, as they are easily accessible in peripheral blood, can readily be expanded and manipulated in vitro, respond to microbial infections in vivo and can be exploited for novel tumor immunotherapies. We here review findings that suggest that Vc9/Vd2 T cells, and possibly other unconventional human T cells, play an important role in bridging innate and adaptive immunity by promoting the activation and differentiation of various types of antigen-presenting cells (APCs) and even turning into APCs themselves, and thereby pave the way for antigen-specific effector responses and long-term immunological memory. Although the direct physiological relevance for most of these mechanisms still needs to be demonstrated in vivo, these findings may have implications for novel therapies, diagnostic tests and vaccines.Ó 2015 Published by Elsevier Inc. Introduction cd T cells represent a third lineage of lymphocytes expressingre-arranged antigen receptors that co-evolved with 'classical' B cells and ab T cells over 400 million years, arguing for a crucial and non-redundant contribution of each lymphocyte to effective immune responses, and hence the evolutionary survival of all jawed vertebrate species [1]. 30 years have passed since the accidental and unexpected cloning of the cd T cell receptor (TCR) and the subsequent realization that ab T cells and cd T cells are fundamentally different with respect to the types of antigens they recognize and the distinct effector functions triggered upon such recognition. However, the manifold contributions of cd T cells to homeostasis, inflammation, infection and tumor surveillance have historically been neglected and are only beginning to be integrated into comprehensive models of the immune system [1][2][3][4][5][6][7].1. Innate-like pattern recognition by human Vc9/Vd2 T cells Like other 'unconventional' T cells carrying an ab TCR such as mucosal-associated invariant T (MAIT) cells and natural killer T (NKT) cells, cd T cells are characterized by a markedly restrictedTCR usage that allows them to recognize self and non-self molecules in the absence of classical antigen presentation via MHC I or MHC II. Vc9/Vd2 + cd T cells represent the major cd T cell subset in human peripheral blood where they typically comprise 1-5% in healthy adults [8]. In many microbial infections, Vc9/Vd2 T cells increase locally and/or systemically [9,10] and can reach in excess of 50% of all peripheral T cells within a matter of days [11], revealing a fundamental role of this unconventional T cell population in acute disease and suggesting their exploitation for diagnostic and therapeutic purposes [12][13][14]. Vc9/Vd2 T cells uniformly respond to a class of low molecular weight molecules often referred to as 'phosphoantigens' that represent metabolites of the isoprenoid biosynthesis...

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Section: Innate-like Pattern Recognition By Human Vc9/vd2 T Cellsmentioning

confidence: 99%

mentioning

confidence: 99%

Human Vγ9/Vδ2 T cells: Innate adaptors of the immune system

Tyler

Doherty

Moser

et al. 2015

Cellular Immunology

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“…For example, iNKT cells are activated by lipids presented by CD1d molecules, 1 whereas certain gd T cells are directly activated by 'danger signals' such as the small microbial product isopentenyl pyrophosphate. 2 Their limited ligand discrimination and relatively larger clonal size allow innate T cells to mount earlier responses than conventional T cells. In comparison with conventional T cells, innate T-cell populations develop by a distinct ontogenic pathway and preferentially home to specific tissues.…”

Section: Ertain Subpopulations Of T Lymphoctyesmentioning

confidence: 99%

“…1 In the absence of IL-10, spontaneous mucosal autoimmunity develops, while the effect on systemic autoimmunity is far more muted. 2 In this issue of Immunology and Cell Biology, however, Lesage and colleagues 3 have uncovered an extra layer of complexity to the role of IL-10 in immune regulation.…”

Section: Autoimmunitymentioning

confidence: 99%

Bacteria, mucosal‐associated invariant T cells and MR1

Chua

Hansen

2010

Immunol Cell Biol

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“…Preferential stimulation by a common microbial isoprenoid metabolite allows responses to a broad array of pathogens through this pathway. 11,12 It has long been known that cd T cells are not MHC restricted and that they can recognize non-peptide antigens, but it remained unclear whether they bind antigen in a manner similar to ab T cells. It was unknown whether they required an antigen-presenting molecule, and if so, the type of molecule was also unknown.…”

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confidence: 99%

A fat story—antigen presentation by butyrophilin 3A1 to γδ T cells

Esser

2013

Cell Mol Immunol

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Microbial isoprenoid biosynthesis and human γδ T cell activation

Cited by 261 publications

References 68 publications

Human Vγ9/Vδ2 T cells: Innate adaptors of the immune system

Human Vγ9/Vδ2 T cells: Innate adaptors of the immune system

Bacteria, mucosal‐associated invariant T cells and MR1

A fat story—antigen presentation by butyrophilin 3A1 to γδ T cells

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