Natural killer T cells recognize diacylglycerol antigens from pathogenic bacteria

Kinjo, Yuki; Tupin, Emmanuel; Wu, Dawei; Fujio, Masakazu; Garcia-Navarro, Raquel; Benhnia, Mohammed Rafii‐El‐Idrissi; Zajonc, Dirk M.; Ben-Menachem, Gil; Ainge, Gary D.; Painter, Gavin F.; Khurana, Archana; Hoebe, Kasper; Behar, Samuel M.; Beutler, Bruce; Wilson, Ian A.; Tsuji, Moriya; Sellati, Timothy J.; Wong, Chi Huey; Kronenberg, Mitchell

doi:10.1038/ni1380

Cited by 580 publications

(569 citation statements)

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“…Whereas the ability of some previously described ligands of microbial origin -Plasmodium (and Trypanosoma) glycosylphosphatidylinositol (GPI) and Mycobacterium phosphatidylinositol mannoside (PIM) -to activate iNKT cells has been questioned, recent work has rigorously demonstrated that GSL-1 from Sphingomonas and BbGL-II from Borrelia undoubtedly stimulate NKT cells in a CD1d-dependent manner [49,[63][64][65]. It remains to be determined whether direct recognition of these glycolipids by iNKT cells is responsible for the iNKT cell-dependent anti-bacterial activity noted during infection with these bacteria [49,63].…”

Section: Exogenous Inkt Cell Antigensmentioning

confidence: 99%

“…iNKT cells have been shown to directly recognize α-linked glycosphingolipids and diacylglycerol antigens that are expressed by bacteria such as Sphingomonas, Ehrlichia and Borrelia burgdorferi in a CD1d-dependent manner [49,[63][64][65] (Figure 1C). The biological response to these glycolipid antigens includes the production of IFNγ and IL-4 by iNKT cells.…”

Section: How Do Inkt Cells Get Activated? Cognate Recognition and Actmentioning

confidence: 99%

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CD1d-restricted iNKT cells, the ‘Swiss-Army knife’ of the immune system

Matsuda

Mallevaey

Scott‐Browne

et al. 2008

Current Opinion in Immunology

355

399

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SummaryNatural Killer T cells are a distinct lymphocyte lineage that regulates a broad range of immune responses. NKT cells recognize glycolipids presented by the non-classical MHC molecule CD1d. Structural insight into the TCR/glycolipid/CD1d tri-complex has revealed an unusual and unexpected mode of recognition. Recent studies have also identified some of the signaling events during NKT cell development that give NKT cells their innate phenotype. Pathogen-derived glycolipid antigens continue to be found, and new mechanisms of NKT cell activation have been described. Finally, NKT cells have been shown to be remarkably versatile in function during various immune responses. Whether these extensive functional capacities can be attributed to a single population sensitive to environmental cues or if functionally distinct NKT cell subpopulations exist remains unresolved.

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Section: Exogenous Inkt Cell Antigensmentioning

confidence: 99%

Section: How Do Inkt Cells Get Activated? Cognate Recognition and Actmentioning

confidence: 99%

CD1d-restricted iNKT cells, the ‘Swiss-Army knife’ of the immune system

Matsuda

Mallevaey

Scott‐Browne

et al. 2008

Current Opinion in Immunology

355

399

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“…Type 1 and type 2 NKT cells also express a number of NK cell stimulatory receptors, such as NK1.1 in mice and NKG2C and NKG2D in humans. While iNKT cells recognize a number of self [147,148] and microbial [149][150][151] glycosphingolipids, most of our understanding of NKT cells comes from studies of murine and human iNKT cells stimulated with the xenogeneic glycolipid, agalactosylceramide (a-GC). Upon activation with a-GC in vitro, iNKT cells can kill target cells and secrete a diverse range of growth factors and cytokines [144][145][146].…”

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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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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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“…Bacteria such as Sphingomonas, Ehrlichia and Borrelia synthesize lipid antigens that form antigenic complexes with CD1d and stimulate iNKT cells [11,12,30]. These bacteria reach Ly, where they release the antigenic lipids.…”

Section: Lipid Traffic Within Cellsmentioning

confidence: 99%

“…Whether they are transported by cytoplasmic LTP remains to be investigated. These two glycolipid antigens can also be released by infected cells and become internalized by non-infected CD1-positive APC, thus allowing their cross-presentation [29].Bacteria such as Sphingomonas, Ehrlichia and Borrelia synthesize lipid antigens that form antigenic complexes with CD1d and stimulate iNKT cells [11,12,30]. These bacteria reach Ly, where they release the antigenic lipids.…”

mentioning

confidence: 99%

The cellular and biochemical rules of lipid antigen presentation

2009

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The recognition of both protein and lipid antigens follows similar strategies that rely on different molecular mechanisms. APC present lipid antigens exploiting the same mechanisms implicated in lipid translocation, lipoprotein assembly and lipid degradation. An important issue is how the lipid structure contributes to antigenicity. Lipid hydrophobicity influences the modes of internalization by APC, the trafficking through different membrane compartments, the binding to CD1 molecules and the stability of antigenic complexes. Some glycolipids with large hydrophilic parts require processing of the sugar moieties exerted by lysosomal hydrolases. Finally, extraction of lipids from membranes, their solubilization and loading on CD1 molecules are facilitated by the same lysosomal lipid-binding proteins that are also instrumental in lipid catabolism. More recent investigations reveal how lipid-specific immunity is regulated during infections. In this review we describe the main cellular and biochemical rules of lipid antigen presentation and discuss their implications in anti-microbial and autoimmune responses.Key words: Antigen recognition . CD1 . Lipid antigens . TCR IntroductionMembers of the MHC or CD1 families present protein and lipid antigens to T cells, respectively. CD1 molecules are differentially expressed by a variety of cell types including DC, B cells, monocytes, Langerhans cells, stellate hepatic cells, epithelial cells, microglial cells and keratinocytes. In humans, five genes (CD1A, B, C, D and E) encode CD1 proteins. CD1a, CD1b, CD1c and CD1d molecules reach the plasma membrane and are involved in lipid presentation to T cells, whereas CD1e remains intracellular and is involved in lipid processing. Lipid-specific T cells express a variety of TCR heterodimers, with the exception of invariant NKT (iNKT) cells, a CD1d-restricted population that uses a semi-invariant TCR (invariant Va24-Ja18 and variable Vb11 chains in humans, invariant Va14-Ja18 and variable Vb8.2, Vb7 or Vb2 chains in mice).Proteins become antigenic after a series of events starting with partial degradation by the cellular machinery represented by the proteasome or by proteases located in lysosomes (Ly) and endoplasmic reticulum (ER). This immunological function, commonly known as antigen processing, leads to the generation of peptide fragments that are carried to the proximity of MHC molecules with which they form antigenic complexes. A similar scheme applies to the presentation of lipid antigens. Lipids derived from extracellular routes are internalized or alternatively, self-lipid antigens are synthesized within the APC. These lipids are then transported into the cellular compartments where CD1 molecules traffic and after loading onto CD1, form antigenic complexes.The physicochemical properties of lipids and peptides impose the utilization of different strategies by the APC to digest, transport and load each of these classes of molecules. Antigenicity of lipids is achieved with the participation of extracellular and intracellular li...

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Natural killer T cells recognize diacylglycerol antigens from pathogenic bacteria

Cited by 580 publications

References 48 publications

CD1d-restricted iNKT cells, the ‘Swiss-Army knife’ of the immune system

CD1d-restricted iNKT cells, the ‘Swiss-Army knife’ of the immune system

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

The cellular and biochemical rules of lipid antigen presentation

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