Recognition of microbial and mammalian phospholipid antigens by NKT cells with diverse TCRs
| Autor: | Susanna Cardell, Dale I. Godfrey, Catarina F. Almeida, Gurdyal S. Besra, Raju V. V. Tatituri, Gerald F. Watts, Veemal Bhowruth, Jamie Rossjohn, Samuel M. Behar, Fong-Fu Hsu, Nathaniel S. Barton, Alissa C. Rothchild, Michael B. Brenner, Liam R. Cox, Lothar Eggeling, Manfred Brigl |
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| Rok vydání: | 2013 |
| Předmět: |
Cardiolipins
Receptors Antigen T-Cell alpha-beta T cell CD1 Antigen-Presenting Cells Transferases (Other Substituted Phosphate Groups) Galactosylceramides chemical and pharmacologic phenomena Biology Cell Line Mice Bacterial Proteins Antigen medicine Animals Antigen-presenting cell Cells Cultured Phospholipids Mice Knockout Antigens Bacterial Hybridomas Multidisciplinary Macrophages Toll-Like Receptors T-cell receptor Phosphatidylglycerols hemic and immune systems Mycobacterium tuberculosis Biological Sciences Natural killer T cell Corynebacterium glutamicum Mice Inbred C57BL medicine.anatomical_structure Biochemistry CD1D Myeloid Differentiation Factor 88 biology.protein Natural Killer T-Cells lipids (amino acids peptides and proteins) Antigens CD1d Cell activation |
| Zdroj: | Proceedings of the National Academy of Sciences. 110:1827-1832 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.1220601110 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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