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Recognition of microbial and mammalian phospholipid antigens by NKT cells with diverse TCRs

Year: 2013
Type: article
Abstract: CD1d-restricted natural killer T (NKT) cells include two major subgroups. The most widely studied are Vα14Jα18(+) invariant NKT (iNKT) cells that recognize the prototypical α-galactosylceramide antigen, whereas the other major group uses diverse T-cell receptor (TCR) α-and β-chains, does not recognize α-galactosylceramide, and is referred to as diverse NKT (dNKT) cells. dNKT cells play important roles during infection and autoimmunity, but the antigens they recognize remain poorly understood. Here, we identified phosphatidylglycerol (PG), diphosphatidylglycerol (DPG, or cardiolipin), and phosphatidylinositol from Mycobacterium tuberculosis or Corynebacterium glutamicum as microbial antigens that stimulated various dNKT, but not iNKT, hybridomas. dNKT hybridomas showed distinct reactivities for diverse antigens. Stimulation of dNKT hybridomas by microbial PG was independent of Toll-like receptor-mediated signaling by antigen-presenting cells and required lipid uptake and/or processing. Furthermore, microbial PG bound to CD1d molecules and plate-bound PG/CD1d complexes stimulated dNKT hybridomas, indicating direct recognition by the dNKT cell TCR. Interestingly, despite structural differences in acyl chain composition between microbial and mammalian PG and DPG, lipids from both sources stimulated dNKT hybridomas, suggesting that presentation of microbial lipids and enhanced availability of stimulatory self-lipids may both contribute to dNKT cell activation during infection.
DOI: 10.1073/pnas.1220601110
Authors: Raju V. V. Tatituri, Gerald F. M. Watts, Veemal Bhowruth, Nathaniel Barton, Alissa Rothchild, Fong-Fu Hsu, Catarina F. Almeida, Liam R. Cox, Lothar Eggeling, Susanna Cardell, Jamie Rossjohn, Dale I. Godfrey, Samuel M. Behar, Gurdyal S. Besra, Michael B. Brenner, Manfred Brigl
Institutions: Brigham and Women's Hospital, Harvard University, Washington University in St. Louis, The University of Melbourne, University of Birmingham, Forschungszentrum Jülich, University of Gothenburg, Monash University
Language: English
Subfield: Immunology
Open Access status: green
Awards: Diabetes Research & Training Center, G2051891711, G2275510897, G2368700977, A Resource for Biomedical Mass Spectrometry, G4561854442, CD1d and NKT Cell Activation and Function in Infection, Phospholipid-Derived Mediators and Insulin Secretion, The effect of type I IFN and IL-12 signaling on T cell immunity to tuberculosis, CD1d-restricted NKT cells in microbial infection, Novel invariant NKT cell agonists as adjuvants for antigen specific T and B cell responses., CD1d and NKT Cell Activation and Function in Infection, T LYMPHOCYTE RECOGNITION, Pathways of Antigen Presentation by CD1, G766674393, Cd1d regulation and its effect on NKT cell activation, Diabetes Research Center
OpenAlex ID: W2055527240
FWCI: 6.016
Cites: 36
Cited by: 123
Related to: 10