Natural killer t cells recognize diacylglycerol antigens from pathogenic bacteria

ABSTRACT Natural killer T (NKT) cells recognize glycosphingolipids presented by CD1d molecules and have been linked to defense against microbial infections. Previously defined foreign

glycosphingolipids recognized by NKT cells are uniquely found in nonpathogenic sphingomonas bacteria. Here we show that mouse and human NKT cells also recognized glycolipids, specifically a

diacylglycerol, from _Borrelia burgdorferi_, which causes Lyme disease. The _B. burgdorferi_–derived, glycolipid-induced NKT cell proliferation and cytokine production and the antigenic

potency of this glycolipid was dependent on acyl chain length and saturation. These data indicate that NKT cells recognize categories of glycolipids beyond those in sphingomonas and suggest

that NKT cell responses driven by T cell receptor–mediated glycolipid recognition may provide protection against diverse pathogens. Access through your institution Buy or subscribe This is a

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MYCOBACTERIAL DIACYL TREHALOSES REVEAL DIFFERENTIAL RECOGNITION BY HUMAN T CELL RECEPTORS AND THE C-TYPE LECTIN MINCLE Article Open access 21 January 2021 DEVELOPMENT OF POTENTIAL

IMMUNOMODULATORY LIGANDS TARGETING NATURAL KILLER T CELLS INSPIRED BY GUT SYMBIONT-DERIVED GLYCOLIPIDS Article Open access 01 April 2025 ROLES OF NATURAL KILLER CELLS IN IMMUNITY TO CANCER,

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of Connecticut Health Science Center, Farmington, Connecticut) for _B. burgdorferi_–infected ticks; E. Janssen and S. McBride (La Jolla Institute for Allergy & Immunology, La Jolla,

California) for _Trif_Lps2/Lps2 mice; V. Kumar (Torrey Pines Institute for Molecular Studies, San Diego, California) for the sulfatide-reactive T cell hybridoma; N. Nagarajan, R. Severins,

Y.W. Zhu (La Jolla Institute for Allergy & Immunology, La Jolla, California) and P. Rogers (Gemini Science, San Diego, California) for technical assistance; and G. Kim (La Jolla

Institute for Allergy & Immunology, La Jolla, California) and M.A. Poles (New York University School of Medicine, New York, New York) for suggestions. Supported by the National

Institutes of Health (AI45053 and AI71922 to M.K.; GM62116 to M.K. and I.A.W.; GM44154 to C.-H.W.; AI054546 to T.J.S.; CA58896 to I.A.W.; and AI062842 to M.T.), the Arthritis Foundation

(T.J.S.) and the Cancer Research Institute (Y.K.). AUTHOR INFORMATION Author notes * Mohammed Rafii-El-Idrissi Benhnia Present address: Division of Vaccine Discovery, La Jolla Institute for

Allergy & Immunology, La Jolla, California, 92037, USA * Dirk M Zajonc Present address: Division of Cellular Biology, La Jolla Institute for Allergy & Immunology, La Jolla,

California, 92037, USA * Gil Ben-Menachem Present address: Paramount Biosciences, Cambridge, Massachusetts, 02138, USA * Yuki Kinjo and Emmanuel Tupin: These authors contributed equally to

this work. AUTHORS AND AFFILIATIONS * Division of Developmental Immunology, La Jolla Institute for Allergy & Immunology, La Jolla, 92037, California, USA Yuki Kinjo, Emmanuel Tupin, 

Archana Khurana & Mitchell Kronenberg * Department of Chemistry and Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, 92037, California, USA Douglass Wu, 

Masakazu Fujio & Chi-Huey Wong * HIV and Malaria Vaccine Program, Aaron Diamond AIDS Research Center, Rockefeller University, New York, 10016, New York, USA Raquel Garcia-Navarro & 

Moriya Tsuji * Center for Immunology and Microbial Disease, Albany Medical College, Albany, 12208, New York, USA Mohammed Rafii-El-Idrissi Benhnia & Timothy J Sellati * Department of

Molecular Biology and Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, 92037, California, USA Dirk M Zajonc & Ian A Wilson * Laboratory of Developmental

and Molecular Immunity, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, 20892, Maryland, USA Gil Ben-Menachem * Carbohydrate Chemistry

Team, Industrial Research, Gracefield Research Center, Lower Hutt, 6008, New Zealand Gary D Ainge & Gavin F Painter * Department of Immunology, The Scripps Research Institute, La Jolla,

92037, California, USA Kasper Hoebe & Bruce Beutler * Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital and Harvard Medical School, Boston, 02115,

Massachusetts, USA Samuel M Behar Authors * Yuki Kinjo View author publications You can also search for this author inPubMed Google Scholar * Emmanuel Tupin View author publications You can

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Mohammed Rafii-El-Idrissi Benhnia View author publications You can also search for this author inPubMed Google Scholar * Dirk M Zajonc View author publications You can also search for this

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Ian A Wilson View author publications You can also search for this author inPubMed Google Scholar * Moriya Tsuji View author publications You can also search for this author inPubMed Google

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inPubMed Google Scholar * Mitchell Kronenberg View author publications You can also search for this author inPubMed Google Scholar CONTRIBUTIONS Y.K. and E.T. designed and did most of the

experiments and prepared the manuscript; D.W., M.F. and C.-H.W. synthesized the BbGL-II compounds and helped with the manuscript; R.G.-N. and M.T. did the human NKT cell experiments; M.R.B.,

T.J.S. and E.T. did the experiments with live bacteria; D.M.Z. and I.A.W. did the molecular modeling of the binding of BbGL-IIc in the CD1d structure and helped with the manuscript; G.B.-M.

provided purified BbGL-I and BbGL-II; G.D.A. and G.F.P. provided the PIM4 compounds; A.K. prepared CD1d proteins; K.H. and B.B. generated the _Trif_Lps2/Lps2 mice; S.M.B. generated the

hybridoma 24.9E; and M.K. provided overall supervision, helped design all the experiments and prepared the manuscript. CORRESPONDING AUTHOR Correspondence to Mitchell Kronenberg. ETHICS

DECLARATIONS COMPETING INTERESTS The authors declare no competing financial interests. SUPPLEMENTARY INFORMATION SUPPLEMENTARY FIG. 1 Additional Vα14_i_ NKT cell hybridomas respond to _B.

burgdorferi_ glycolipids. (PDF 21 kb) SUPPLEMENTARY FIG. 2 CD1d reactive T cell hybridomas that do not express Vα14_i_ are not BbGl-2 reactive. (PDF 14 kb) SUPPLEMENTARY FIG. 3 PIM4 does not

stimulate Vα14_i_ NKT cells _in vivo_. (PDF 29 kb) SUPPLEMENTARY FIG. 4 BbGL compounds do not cause inflammatory cytokine production by DC. (PDF 45 kb) SUPPLEMENTARY FIG. 5 TRIF-independent

activation of Vα14_i_ NKT cells by _B. burgdorferi_ antigen. (PDF 20 kb) SUPPLEMENTARY METHODS (PDF 323 KB) RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS

ARTICLE Kinjo, Y., Tupin, E., Wu, D. _et al._ Natural killer T cells recognize diacylglycerol antigens from pathogenic bacteria. _Nat Immunol_ 7, 978–986 (2006).

https://doi.org/10.1038/ni1380 Download citation * Received: 14 June 2006 * Accepted: 25 July 2006 * Published: 20 August 2006 * Issue Date: 01 September 2006 * DOI:

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