Kinetics and Cellular Site of Glycolipid Loading Control the Outcome of Natural Killer T Cell Activation

Overview

Journal Immunity

Publisher Cell Press

Specialty Allergy & Immunology

Date 2009 Jun 23

PMID 19538930

Citations 106

Authors

Jin S Im

Pooja Arora

Gabriel Bricard

Alberto Molano

Manjunatha M Venkataswamy

Ian Baine

Elliot S Jerud

Michael F Goldberg

Andres Baena

Karl O A Yu

Rachel M Ndonye

Amy R Howell

Weiming Yuan

Peter Cresswell

Young-Tae Chang

Petr A Illarionov

Gurdyal S Besra

Steven A Porcelli

Affiliations

Soon will be listed here.

Abstract

CD1d-restricted natural killer T cells (NKT cells) possess a wide range of effector and regulatory activities that are related to their ability to secrete both T helper 1 (Th1) cell- and Th2 cell-type cytokines. We analyzed presentation of NKT cell activating alpha galactosylceramide (alphaGalCer) analogs that give predominantly Th2 cell-type cytokine responses to determine how ligand structure controls the outcome of NKT cell activation. Using a monoclonal antibody specific for alphaGalCer-CD1d complexes to visualize and quantitate glycolipid presentation, we found that Th2 cell-type cytokine-biasing ligands were characterized by rapid and direct loading of cell-surface CD1d proteins. Complexes formed by association of these Th2 cell-type cytokine-biasing alphaGalCer analogs with CD1d showed a distinctive exclusion from ganglioside-enriched, detergent-resistant plasma membrane microdomains of antigen-presenting cells. These findings help to explain how subtle alterations in glycolipid ligand structure can control the balance of proinflammatory and anti-inflammatory activities of NKT cells.

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References

Zhou D, Cantu 3rd C, Sagiv Y, Schrantz N, Kulkarni A, Qi X . Editing of CD1d-bound lipid antigens by endosomal lipid transfer proteins. Science. 2003; 303(5657):523-7. PMC: 2918537. DOI: 10.1126/science.1092009. View

Yu K, Im J, Illarionov P, Ndonye R, Howell A, Besra G . Production and characterization of monoclonal antibodies against complexes of the NKT cell ligand alpha-galactosylceramide bound to mouse CD1d. J Immunol Methods. 2007; 323(1):11-23. PMC: 1939826. DOI: 10.1016/j.jim.2007.03.006. View

Borg N, Wun K, Kjer-Nielsen L, Wilce M, Pellicci D, Koh R . CD1d-lipid-antigen recognition by the semi-invariant NKT T-cell receptor. Nature. 2007; 448(7149):44-9. DOI: 10.1038/nature05907. View

Fujio M, Wu D, Garcia-Navarro R, Ho D, Tsuji M, Wong C . Structure-based discovery of glycolipids for CD1d-mediated NKT cell activation: tuning the adjuvant versus immunosuppression activity. J Am Chem Soc. 2006; 128(28):9022-3. DOI: 10.1021/ja062740z. View

Park Y, Lee J, Ko Y, Hong S, Park S . Lipid rafts are required for efficient signal transduction by CD1d. Biochem Biophys Res Commun. 2005; 327(4):1143-54. DOI: 10.1016/j.bbrc.2004.12.121. View

Forestier C, Takaki T, Molano A, Im J, Baine I, Jerud E . Improved outcomes in NOD mice treated with a novel Th2 cytokine-biasing NKT cell activator. J Immunol. 2007; 178(3):1415-25. DOI: 10.4049/jimmunol.178.3.1415. View

Schmieg J, Yang G, Franck R, Tsuji M . Superior protection against malaria and melanoma metastases by a C-glycoside analogue of the natural killer T cell ligand alpha-Galactosylceramide. J Exp Med. 2003; 198(11):1631-41. PMC: 2194137. DOI: 10.1084/jem.20031192. View

Peng W, Martaresche C, Escande-Beillard N, Cedile O, Reynier-Vigouroux A, Boucraut J . Influence of lipid rafts on CD1d presentation by dendritic cells. Mol Membr Biol. 2007; 24(5-6):475-84. DOI: 10.1080/09687680701359408. View

Oki S, Chiba A, Yamamura T, Miyake S . The clinical implication and molecular mechanism of preferential IL-4 production by modified glycolipid-stimulated NKT cells. J Clin Invest. 2004; 113(11):1631-40. PMC: 419488. DOI: 10.1172/JCI20862. View

10.

Buatois V, Baillet M, Becart S, Mooney N, Leserman L, Machy P . MHC class II-peptide complexes in dendritic cell lipid microdomains initiate the CD4 Th1 phenotype. J Immunol. 2003; 171(11):5812-9. DOI: 10.4049/jimmunol.171.11.5812. View

11.

Schrantz N, Sagiv Y, Liu Y, Savage P, Bendelac A, Teyton L . The Niemann-Pick type C2 protein loads isoglobotrihexosylceramide onto CD1d molecules and contributes to the thymic selection of NKT cells. J Exp Med. 2007; 204(4):841-52. PMC: 2118543. DOI: 10.1084/jem.20061562. View

12.

Crowe N, Coquet J, Berzins S, Kyparissoudis K, Keating R, Pellicci D . Differential antitumor immunity mediated by NKT cell subsets in vivo. J Exp Med. 2005; 202(9):1279-88. PMC: 1459911. DOI: 10.1084/jem.20050953. View

13.

Miyake S, Yamamura T . Therapeutic potential of glycolipid ligands for natural killer (NK) T cells in the suppression of autoimmune diseases. Curr Drug Targets Immune Endocr Metabol Disord. 2005; 5(3):315-22. DOI: 10.2174/1568008054863772. View

14.

Behar S, Porcelli S . CD1-restricted T cells in host defense to infectious diseases. Curr Top Microbiol Immunol. 2007; 314:215-50. DOI: 10.1007/978-3-540-69511-0_9. View

15.

Koch M, Stronge V, Shepherd D, Gadola S, Mathew B, Ritter G . The crystal structure of human CD1d with and without alpha-galactosylceramide. Nat Immunol. 2005; 6(8):819-26. DOI: 10.1038/ni1225. View

16.

Bendelac A, Savage P, Teyton L . The biology of NKT cells. Annu Rev Immunol. 2006; 25:297-336. DOI: 10.1146/annurev.immunol.25.022106.141711. View

17.

Bezbradica J, Stanic A, Matsuki N, Bour-Jordan H, Bluestone J, Thomas J . Distinct roles of dendritic cells and B cells in Va14Ja18 natural T cell activation in vivo. J Immunol. 2005; 174(8):4696-705. DOI: 10.4049/jimmunol.174.8.4696. View

18.

Jiang X, Kojo S, Harada M, Ohkohchi N, Taniguchi M, Seino K . Mechanism of NKT cell-mediated transplant tolerance. Am J Transplant. 2007; 7(6):1482-90. DOI: 10.1111/j.1600-6143.2007.01827.x. View

19.

Sagiv Y, Hudspeth K, Mattner J, Schrantz N, Stern R, Zhou D . Cutting edge: impaired glycosphingolipid trafficking and NKT cell development in mice lacking Niemann-Pick type C1 protein. J Immunol. 2006; 177(1):26-30. DOI: 10.4049/jimmunol.177.1.26. View

20.

Lang G, Maltsev S, Besra G, Lang M . Presentation of alpha-galactosylceramide by murine CD1d to natural killer T cells is facilitated by plasma membrane glycolipid rafts. Immunology. 2004; 112(3):386-96. PMC: 1782508. DOI: 10.1111/j.1365-2567.2004.01896.x. View