Tumor Recognition following Vγ9Vδ2 T Cell Receptor Interactions with a Surface F1-ATPase-Related Structure and Apolipoprotein A-I

Scotet, Emmanuel; Martinez, Laurent O.; Grant, Ethan P.; Barbaras, Ronald; Jenö, Paul; Guiraud, Martine; Monsarrat, Bernard; Saulquin, Xavier; Maillet, Sophie; Estève, Jean-Pierre; Lopez, Fréderic; Fougère, Bertrand; Collet, Xavier; Bonneville, Marc; Champagne, Éric

doi:10.1016/j.immuni.2004.11.012

Cited by 267 publications

(223 citation statements)

References 37 publications

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“…73 Recent developments in regards to alternative potential endogenous stress-induced ligands for Vc9Vd2 T cells provide new venues that may reveal how these cellular short-lived substrates can be potentially stabilized and presented extracellularly to the stress surveillance capabilities inherent in these lymphocytes. Scotet and colleagues 74 first reported that tumor recognition by Vc9Vd2 T cells could be mediated by the ectopic expression of ATP synthase/F1-ATPase, which is normally expressed on the internal membrane of mitochondria, and this interaction was enhanced by the cobinding of apolipoprotein A-I that is usually present in serum. Literally along the same vein, it was later observed that shear stress experienced by endothelial cells also led to the translocation of the ATP synthase b chain to the cell surface which resulted in the binding and activation of Vc9Vd2 T cells.…”

Section: Vd2 T Cells: To Know the Complex Burden Of Being Humanmentioning

confidence: 99%

Defining the nature of human γδ T cells: a biographical sketch of the highly empathetic

2012

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The elusive task of defining the character of cd T cells has been an evolving process for immunologists since stumbling upon their existence during the molecular characterization of the a and b T cell receptor genes of their better understood brethren. Defying the categorical rules used to distinctly characterize lymphocytes as either innate or adaptive in nature, cd T cells inhabit a hybrid world of their own. At opposing ends of the simplified spectrum of modes of antigen recognition used by lymphocytes, natural killer and ab T cells are particularly well equipped to respond to the 'missing self' and the 'dangerous non-self', respectively. However, between these two reductive extremes, we are chronically faced with the challenge of making peace with the 'safe non-self' and dealing with the inevitable 'distressed self', and it is within this more complex realm cd T cells excel thanks to their highly empathetic nature. This review gives an overview of the latest insights revealing the unfolding story of human cd T cells, providing a biographical sketch of these unique lymphocytes in an attempt to capture the essence of their fundamental nature and events that influence their life trajectory. What hangs in their balance is their nuanced ability to differentiate the friends from the foe and the pathological from the benign to help us adapt swiftly and efficiently to life's many stresses. Keywords: antigen recognition; danger-associated molecular patterns; gamma delta T cell subsets; immune homeostasis; innate immunity; stress response PROLOGUE Since the time of their accidental discovery during the molecular characterization of the a and b T cell receptor (TCR) genes belonging to their relatively unambiguous brethren, 1 'enigmatic' is still one of the most commonly used adjectives to describe cd T cells. This can be attributed to the fact that these unconventional lymphocytes have thus far been remarkably successful in thwarting most attempts at definition. Much of what we know about T cell biology and function comes from what has been discerned through studies done on ab T cells; however, one thing that is certain is that the majority of the rules governing the lives of ab T cells are surprisingly irrelevant when it comes to understanding the elusive character of cd T cells. Table 1 highlights some of the major differences between these two T cell subsets in humans.Recognition by cd T cells is not typically in the context of classical major histocompatibility complex (MHC) class I or II molecules and neither is antigen processing required. 2,3 These observations are corroborated by the fact that the majority of cd T cells are CD8 and CD4 negative. Crystal structure analysis of the cd TCR determined that the length and conformation of cd TCR resemble immunoglobulins (Ig) more than the ab TCR, which was taken to suggest that antigen recognition by cd T cells may be more similar to the binding of antibody to antigen rather than the MHC/peptide complex recognized by ab T cells. 4 The very basis of foreign antigen rec...

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Section: Vd2 T Cells: To Know the Complex Burden Of Being Humanmentioning

confidence: 99%

Defining the nature of human γδ T cells: a biographical sketch of the highly empathetic

2012

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“…Aminobisphosphonate such as zoledronate may activate Vg9Vd2 T cells indirectly by blocking the mevalonate pathway and consequently promoting intracellular accumulation of isopentenyl pyrophosphate [8]. Recent findings suggest that the mitochondrial F1-ATPase exposed at the surface of the stimulating cells could participate to phosphoantigen presentation and subsequent Vg9Vd2 T-cell activation [12,13]. We and others have described that the synthetic phosphoantigen bromohydrin pyrophosphate (BrHPP, Innate Pharma, Marseilles, France) was able to vigorously expand Vg9Vd2 T cells owing a broad reactivity against tumor cell lines [4,5].…”

Section: Introductionmentioning

confidence: 99%

DNAX accessory molecule‐1 (CD226) promotes human hepatocellular carcinoma cell lysis by Vγ9Vδ2 T cells

et al. 2009

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Human Vc9Vd2 T lymphocytes can be activated by nonpeptidic antigens such as the mevalonate pathway-derived isopentenyl pyrophosphate or synthetic phosphoantigen such as bromohydrin pyrophosphate. They display a strong cytotoxic activity against several tumor types, including hepatocellular carcinoma (HCC). Little is known about the mechanisms underlying Vc9Vd2 T-cell recognition of tumor cells, but there is strong evidence that activating NK receptors play a role in cd T-cell cytotoxicity. In this study, we showed that the two NK receptors DNAX accessory molecule-1 (DNAM-1) and CD96 were expressed by Vc9Vd2 T cells. The ligands Nectin-like-5 specific of both DNAM-1 and CD96, and also Nectin-2, an additional ligand of DNAM-1, were present on all HCC cell lines analyzed. Furthermore, we demonstrated by mAb-mediated masking experiments that cytotoxicity against HCC cells as well as IFN-c production in cd T cells were dependent on DNAM-1. Our experiments indicated that Nectin-like-5 but not Nectin-2 was involved in DNAM-1-dependent cd T-cell functions. We did not reveal a role for CD96 in the killing of HCC cells. Finally, we showed by combined mAb-mediated blockade that DNAM-1 and NKG2D could cooperate in the cell lysis of HCC.

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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%

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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Tumor Recognition following Vγ9Vδ2 T Cell Receptor Interactions with a Surface F1-ATPase-Related Structure and Apolipoprotein A-I

Cited by 267 publications

References 37 publications

Defining the nature of human γδ T cells: a biographical sketch of the highly empathetic

Defining the nature of human γδ T cells: a biographical sketch of the highly empathetic

DNAX accessory molecule‐1 (CD226) promotes human hepatocellular carcinoma cell lysis by Vγ9Vδ2 T cells

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

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