Direct presentation of nonpeptide prenyl pyrophosphate antigens to human γδ T cells

Morita, Craig T.; Beckman, Evan M.; Bukowski, Jack F.; Tanaka, Yoshimasa; Band, Hamid; Bloom, Barry R.; Golan, David E.; Brenner, Michael B.

doi:10.1016/1074-7613(95)90178-7

Cited by 433 publications

(404 citation statements)

References 73 publications

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Section: Introductionmentioning

confidence: 99%

“…In the mouse, cd T cell subsets recognize the non-classical MHC class I molecules T10/T22 [15], and an unknown ligand expressed by keratinocytes [16]. In humans, some Vd1 cd T cells recognize non-classical MHC class I molecules MICA and MICB, and Vc9Vd2 cd T cells have been reported to recognize self and bacterial phosphoantigens, and a complex formed between F1-ATP synthase and apolipoprotein A-1 [5,[17][18][19][20].During mouse NK cell development, lineage markernegative bone marrow progenitors develop progressively into CD122 + NK1.1 -DX5 -committed NK progenitors, CD122 + NK1.1 + DX5 -immature NK cells and finally CD122 + NK1.1 + DX5 + mature NK cells, all of which can be found in the bone marrow. At the immature DX5 -stage, NK cells express multiple NK receptors including CD94/NKG2, NKG2D and NKp46, but are unable to perform granule-mediated cytotoxicity [21][22][23].…”

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confidence: 99%

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Germ‐line and rearranged Tcrd transcription distinguish bona fide NK cells and NK‐like γδ T cells

et al. 2007

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NK cells and cd T cells are distinct subsets of lymphocytes that contextually share multiple phenotypic and functional characteristics. However, the acquisition and the extent of these similarities remain poorly understood. Here, using T cell receptor d locus-histone 2B-enhanced GFP (Tcrd-H2BEGFP) reporter mice, we show that germline transcription of Tcrd occurs in all maturing NK cells. We also describe a population of mouse NK-like cells that are indistinguishable from "bona fide" NK cells using standard protocols. Requirements for V(D)J recombination and a functional thymus, along with very low-level expression of surface TCRcd but high intracellular CD3, define these cells as cd T cells. "NK-like cd T cells" are CD127 + , have a memory-activated phenotype, express multiple NK cell receptors and readily produce interferon-c in response to IL-12/IL-18 stimulation. The close phenotypic resemblance between NK cells and NK-like cd T cells is a source of experimental ambiguity in studies bridging NK and T cell biology, such as those on thymic NK cell development. Instead, it ascribes chronic TCRcd engagement as a means of acquiring NK-like function. IntroductionClassification of NK cells and some cd T cell subsets as innate immune cells is argued by their recognition and response to self ligands and microbial molecules without any requirement for prior specific immunization [1][2][3][4][5]. NK cells are mediators of immunity against various infectious diseases and tumor cells, performing direct cell-mediated cytotoxicity and producing cytokines in response to cell-associated and soluble stimuli [6,7]. They additionally shape adaptive immune responses, mainly through the production of cytokines [8]. Their activation is regulated through germ-line-encoded receptors including NKG2D, the natural cytotoxicity receptors and inhibitory receptors for MHC class I, many of which recognize self-encoded ligands [9][10][11]. Most cd T cell subsets are unconventional T cells that -similar to CD1d-restricted Va14i NKT cells, MR1-restricted MAIT cells and certain populations of CD8 + T cells -are not restricted to classical MHC class I-or MHC class II-bearing specific peptides [2,3]. They have heterogeneous effector functions associated with differential TCRcd usage. Roles have been described in immunity against infectious pathogens and tumors [12] and cd T cells have been strongly implicated in immunosuppressive regulation of the immune system and in the process of wound healing [13,14]. Using TCR transfer experiments, or direct ligand binding, TCRcd ligands have been described for a small number of subsets [5]. In the mouse, cd T cell subsets recognize the non-classical MHC class I molecules T10/T22 [15], and an unknown ligand expressed by keratinocytes [16]. In humans, some Vd1 cd T cells recognize non-classical MHC class I molecules MICA and MICB, and Vc9Vd2 cd T cells have been reported to recognize self and bacterial phosphoantigens, and a complex formed between F1-ATP synthase and apolipoprotein A-1 [5,[17][18][19][20].Du...

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Section: Introductionmentioning

confidence: 99%

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confidence: 99%

Germ‐line and rearranged Tcrd transcription distinguish bona fide NK cells and NK‐like γδ T cells

et al. 2007

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“…These phosphoantigens are usually natural metabolites of isoprenoid biosynthesis in host cells, which include IPP, (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate, dimethylallyl pyrophosphate (DMAPP) 53,54 and bromohydrin pyrophosphate. 55 These phosphoantigens can be presented by T cells, monocytes and various antigen-presenting cells (APCs), such as DCs and B cells, 56,57 through expression of CD1d 58,59 and as-yet unknown non-MHC molecules on host cells. 60 The clinical applications of phosphoantigens in cd-T cell-based therapy will be discussed in a later part of this review.…”

Section: Host Cell-derived Signalsmentioning

confidence: 99%

γδ-T cells: an unpolished sword in human anti-infection immunity

et al. 2012

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cd-T cells represent a small population of immune cells, but play an indispensable role in host defenses against exogenous pathogens, immune surveillance of endogenous pathogenesis and even homeostasis of the immune system. Activation and expansion of cd-T cells are generally observed in diverse human infectious diseases and correlate with their progression and prognosis. cd-T cells have both 'innate' and 'adaptive' characteristics in the immune response, and their anti-infection activities are mediated by multiple pathways that are under elaborate regulation by other immune components. In this review, we summarize the current state of the literature and the recent advancements in cd-T cell-mediated immune responses against common human infectious pathogens. Although further investigation is needed to improve our understanding of the characteristics of different cd-T cell subpopulations under specific conditions, cd-T cell-based therapy has great potential for the treatment of infectious diseases.

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“…However, in some cases it has been shown that Ags must be presented to be stimulatory for cd T cells. 17 These presented Ags tend to be small, and in soluble form might not be capable of TCR cross-linking, a prerequisite for activation via immunoreceptors. Whether any Ags in solution can be recognized and can trigger responses of cd T cells is not yet known, although this seems likely when such Ags are multivalent.…”

Section: Mechanism Of Ligand Recognitionmentioning

confidence: 99%

“…105 This may be more understandable considering that these small molecules appear to be presented on the surface of target cells 17,106,107 and thus might be 'seen' in a certain context. However, the mechanism of presentation remains mostly unclear, and it might vary between individual Ags.…”

Section: Non-peptidic Agsmentioning

confidence: 99%

Diversity of γδ T-cell antigens

2012

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In the last two decades, it has become clear that cd T cells recognize a diverse array of antigens including self and foreign, large and small, and peptidic and non-peptidic molecules. In this respect, cd antigens as a whole resemble more the antigens recognized by antibodies than those recognized by ab T cells. Because of this antigenic diversity, no single mechanism-such as the major histocompatibility complex (MHC) restriction of ab T cells-is likely to provide a basis for all observed T-cell antigen receptor (TCR)-dependent cd T-cell responses. Furthermore, available evidence suggests that many individual cd T cells are poly-specific, probably using different modes of ligand recognition in their responses to unrelated antigens. While posing a unique challenge in the maintenance of self-tolerance, this broad reactivity pattern might enable multiple overlapping uses of cd T-cell populations, and thus generate a more efficient immune response.

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Direct presentation of nonpeptide prenyl pyrophosphate antigens to human γδ T cells

Cited by 433 publications

References 73 publications

Germ‐line and rearranged Tcrd transcription distinguish bona fide NK cells and NK‐like γδ T cells

Germ‐line and rearranged Tcrd transcription distinguish bona fide NK cells and NK‐like γδ T cells

γδ-T cells: an unpolished sword in human anti-infection immunity

Diversity of γδ T-cell antigens

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