Journal Article

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

Brigl, Manfred, Almeida, Catarina F., Besra, Gurdyal S., Eggeling, Lothar, Godfrey, Dale I., Tatituri, Raju V. V., Barton, Nathaniel, Cardell, Susanna, Behar, Samuel M., Rothchild, Alissa, Watts, Gerald F. M., Rossjohn, Jamie, Bhowruth, Veemal, Brenner, Michael B., Hsu, Fong-Fu, Cox, Liam R.

2013

Overview

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.

• Publisher: National Academy of Sciences,National Acad Sciences
• Subject: activation / adaptive immunity / Animals / Antigen presenting cells / Antigen-Presenting Cells - immunology / Antigen-Presenting Cells - metabolism / Antigens / Antigens, Bacterial - immunology / Antigens, Bacterial - metabolism / Antigens, CD1d - genetics / Antigens, CD1d - immunology / Antigens, CD1d - metabolism / autoimmunity / Bacteria / Bacterial Proteins - genetics / Bacterial Proteins - immunology / Bacterial Proteins - metabolism / Biological Sciences / Cardiolipins - immunology / Cardiolipins - metabolism / cd1 / CD1 antigen presentation / Cell Line / Cells, Cultured / Corynebacterium glutamicum / Corynebacterium glutamicum - genetics / Corynebacterium glutamicum - immunology / Corynebacterium glutamicum - metabolism / distinct / Galactosylceramides - immunology / Galactosylceramides - metabolism / glycolipids / GSTsuji / Gurdyal S.Besra / Hybridomas / Hybridomas - immunology / Hybridomas - metabolism / Infections / innate immunity / innate-like / Kawakami / KazuyoshiKawakami / killer t-cells / KNizet / Lipids / Macrophages - immunology / Macrophages - metabolism / Macrophages - microbiology / Mammals / Mice / Mice, Inbred C57BL / Mice, Knockout / Microbiology in the Medical Area / Mikrobiologi inom det medicinska området / Molecules / MoriyaTsuji / Mycobacterium tuberculosis / Mycobacterium tuberculosis - immunology / Mycobacterium tuberculosis - metabolism / Myeloid Differentiation Factor 88 - genetics / Myeloid Differentiation Factor 88 - immunology / Myeloid Differentiation Factor 88 - metabolism / Natural killer T cells / Natural Killer T-Cells - immunology / Natural Killer T-Cells - metabolism / Phosphatidylglycerols - immunology / Phosphatidylglycerols - metabolism / Phospholipids / Phospholipids - immunology / Phospholipids - metabolism / population / Reactivity / receptor / Receptors, Antigen, T-Cell, alpha-beta - immunology / Receptors, Antigen, T-Cell, alpha-beta - metabolism / repertoire / sulfatide / T cell antigen receptors / T cell receptors / T lymphocytes / Toll-Like Receptors - immunology / Toll-Like Receptors - metabolism / Transferases (Other Substituted Phosphate Groups) - genetics / Transferases (Other Substituted Phosphate Groups) - immunology / Transferases (Other Substituted Phosphate Groups) - metabolism / type II natural killer T cell / VBesra / VictorNizet