T Cell Activation by CD1 and Lipid Antigens: 314 (Current Topics in Microbiology and Immunology)

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Tracking the response of natural killer T cells to a glycolipid antigen using CD1d tetramers. Murine CD1d-restricted T cell recognition of cellular lipids. Immunity Differences in the ligand specificity between CD1d-restricted T cells with limited and diverse T-cell receptor repertoire. Recognition of CD1d-restricted antigens by natural killer T cells. Dhodapkar MV, Kumar V. J Immunol. Prevention of autoimmunity by targeting a distinct, noninvariant CD1d-reactive T cell population reactive to sulfatide.

Cutting edge: compartmentalization of Th1-like noninvariant CD1d-reactive T cells in hepatitis C virus-infected liver. Identification of novel glycolipid ligands activating a sulfatide-reactive, CD1d-restricted, type II natural killer T lymphocyte. Eur J Immunol. Dasgupta S, Kumar V. Immunogenetics — Sulfatide, a major lipid component of myelin sheath, activates inflammatory responses as an endogenous stimulator in brain-resident immune cells.

Type II natural killer T cells use features of both innate-like and conventional T cells to recognize sulfatide self antigens. Recognition of lysophosphatidylcholine by type II NKT cells and protection from an inflammatory liver disease. Blood — Inflammation-associated lysophospholipids as ligands for CD1d-restricted T cells in human cancer.

Hepatitis B virus-induced lipid alterations contribute to natural killer T cell-dependent protective immunity. Nat Med. Recognition of lyso-phospholipids by human natural killer T lymphocytes. PLoS Biol. Functionally distinct subsets of CD1d-restricted natural killer T cells revealed by CD1d tetramer staining. Diverse endogenous antigens for mouse NKT cells: self-antigens that are not glycosphingolipids.

CD1b-autoreactive T cells contribute to hyperlipidemia-induced skin inflammation in mice

Type II Natural Killer T cells that recognize sterol carrier protein 2 are implicated in vascular inflammation in the rat model of systemic connective tissue diseases. Am J Pathol. Nishioka YM S. Tomaru, U. Ishizu, A. The role of invariant natural killer T cells in microbial immunity. J Infect Chemother. Immunity — Steady-state production of IL-4 modulates immunity in mouse strains and is determined by lineage diversity of iNKT cells.

A Microbial Glycolipid Functions as a New Class of Target Antigen for Delayed-type Hypersensitivity

Unique invariant natural killer T cells promote intestinal polyps by suppressing TH1 immunity and promoting regulatory T cells. Mucosal Immunol. Surface receptors identify mouse NK1. Molecular profiling reveals distinct functional attributes of CD1d-restricted natural killer NK T cell subsets. Mol Immunol. Self glycolipids as T-cell autoantigens. Dendritic cells and anergic type I NKT cells play a crucial role in sulfatide-mediated immune regulation in experimental autoimmune encephalomyelitis.

Involvement of sulfatide in beta cells and type 1 and type 2 diabetes.

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Diabetologia — Treatment with sulfatide or its precursor, galactosylceramide, prevents diabetes in NOD mice. Autoimmunity — NKT cells stimulated by long fatty acyl chain sulfatides significantly reduce the incidence of type 1 diabetes in nonobese diabetic mice [corrected]. Administration of sulfatide to ameliorate type I diabetes in non-obese diabetic mice.

NKT cell networks in the regulation of tumor immunity. A brief review of clinical trials involving manipulation of invariant NKT cells as a promising approach in future cancer therapies. Cent Eur J Immunol.


Possible therapeutic application of targeting type II natural killer T cell-mediated suppression of tumor immunity. Wang Y, Cardell SL. The yin and yang of invariant natural killer t cells in tumor immunity-suppression of tumor immunity in the intestine. Gut — The functions of type I and type II natural killer T cells in inflammatory bowel diseases.

Inflamm Bowel Dis. Gastroenterology —34 e Obesity and cancer: the role of adipose tissue and adipo-cytokines-induced chronic inflammation. J Cancer — Adipose tissue invariant NKT cells protect against diet-induced obesity and metabolic disorder through regulatory cytokine production. Natural killer T cells are involved in adipose tissues inflammation and glucose intolerance in diet-induced obese mice. Arterioscler Thromb Vasc Biol.

J Clin Invest. Natural killer T cells in adipose tissue prevent insulin resistance. Activation of invariant natural killer T cells by lipid excess promotes tissue inflammation, insulin resistance, and hepatic steatosis in obese mice. Type II NKT cells stimulate diet-induced obesity by mediating adipose tissue inflammation, steatohepatitis and insulin resistance. Int J Mol Sci. Kumar V. NKT-cell subsets: promoters and protectors in inflammatory liver disease.

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  • J Hepatol. Sulfatide-mediated activation of type II natural killer T cells prevents hepatic ischemic reperfusion injury in mice. Gastroenterology — Inhibition of type I natural killer T cells by retinoids or following sulfatide-mediated activation of type II natural killer T cells attenuates alcoholic liver disease in mice. Hepatology — Brigl M, Brenner MB. How invariant natural killer T cells respond to infection by recognizing microbial or endogenous lipid antigens. Semin Immunol.

    Critical proinflammatory and anti-inflammatory functions of different subsets of CD1d-restricted natural killer T cells during Trypanosoma cruzi infection. Infect Immun. Activation of invariant NKT cells by the helminth parasite schistosoma mansoni. Sulfatide attenuates experimental Staphylococcus aureus sepsis through a CD1d-dependent pathway. Activation of a nonclassical NKT cell subset in a transgenic mouse model of hepatitis B virus infection. Sulfatide administration leads to inhibition of HIV-1 replication and enhanced hematopoeisis.

    J Stem Cells — Immunol Cell Biol. A major fraction of human bone marrow lymphocytes are Th2-like CD1d-reactive T cells that can suppress mixed lymphocyte responses.


    Gaucher disease gene GBA functions in immune regulation. The underrecognized progressive nature of NS Gaucher disease and assessment of cancer risk in patients. Am J Hematol. Activation of mouse iNKT hybridomas 1. Individual amino acid mutations in CD1d are indicated. Experiment was performed twice, while measuring each condition in triplicate. In contrast to earlier studies we could now show that cattle express CD1d protein that is able to traffic to the cell surface for antigen display [15].

    In vitro binding studies indicated that glycolipids that exceed the alkyl chain length of C 18 do not bind to boCD1d. The importance of the Asp sidechain has further been demonstrated by mutagenesis studies using mouse CD1d. While mouse and human iNKT cells are evolutionary conserved and generally respond to the same antigens, this is not true for the more recently identified microbial antigens.

    Therefore, it is possible that bovine pathogens differ in their lipid composition compared to human and mouse pathogens and as a result cattle have evolved lipid-reactive and boCD1d-restricted T cells that are likely different from human or mouse iNKT cells. Therefore, boCD1d cannot present the same range of antigen as human and mouse CD1d can. The only other species for which CD1 crystal structures are available is chicken. Both chicken ch CD and chCD have been crystallized with endogenously bound lipids and the structures reveal two extremes in terms of size and shape of the hydrophobic binding groove, which dictates the type of lipids that can be presented by CD1 [36] , [37].

    While chCD has a primitive single pore suitable for binding of single chain lipids or fatty acids [37] , chCD has an elaborate binding groove suitable to accommodate dual and possibly tri-acylated lipids [36].

    Antigen Presentation, T Cell Activation and Deactivation

    Thus changes in size and shape of the binding groove likely reflect the encounter with different lipid structures from different pathogens during the course of CD1 evolution. It is conceivable that this allows the accommodation of small acyl chain modifications, such as hydroxyl or methyl groups, which are found in different lipids or fatty acids such as tuberculostearic acid. Furthermore, lack of human T cell activation by bovine CD1 has also been seen for another bovine CD1 isotype, boCD1b3, which is unable to activate the human CD1b-restricted T cell line LDN5 when presenting glucose monomycolate [10] , indicating that lipid reactive T cells in cattle differ from that of mouse and man.

    Antigen omit map electron density. We would like to thank the staff of the Advanced Light Source, beamline 5. Browse Subject Areas? Click through the PLOS taxonomy to find articles in your field. Abstract NKT cells play important roles in immune surveillance. Introduction CD1 is a family of antigen-presenting molecules that is structurally related to major histocompatibility class I MHC I molecules, but binds and presents lipids, glycolipids and lipopeptides, rather than peptides [1].

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    Protein Crystallization Crystallization was performed in a well format by a nanoliter dispensing liquid handling robot Phoenix, Art Robbins Ltd. Cell Free Antigen Presentation Assay The cell-free Ag presentation assay for stimulation of mouse iNKT cell hybridomas by recombinant mouse, human and bovine CD1d was carried out according to published protocols [25] , [26] with the following modifications. Discussion In contrast to earlier studies we could now show that cattle express CD1d protein that is able to traffic to the cell surface for antigen display [15].

    Supporting Information. Figure S1. Acknowledgments We would like to thank the staff of the Advanced Light Source, beamline 5. References 1. Nat Rev Immunol 5: — View Article Google Scholar 2. Annu Rev Immunol — View Article Google Scholar 3. View Article Google Scholar 4. Current topics in microbiology and immunology 27— View Article Google Scholar 5. Nat Rev Immunol 3: 11— View Article Google Scholar 6. Nat Immunol 4: — View Article Google Scholar 7. J Immunol — View Article Google Scholar 8. View Article Google Scholar 9. Immunogenetics — View Article Google Scholar Nat Rev Immunol 4: — European journal of immunology — J Exp Med — Int Immunol.

    Methods Enzymol — Acta Crystallogr D Biol Crystallogr — Nucleic Acids Res — Acta Crystallogr D — Acta crystallographica Section D, Biological crystallography — Proteins — Nat Immunol 7: — Nature — Nucleic acids research W— Nucleic Acids Res W— Nat Immunol 8: — Immunity 47— Nature 44—

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