title: Recognition of microbial and mammalian phospholipid antigens by NKT cells with diverse TCRs.
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.
authors: Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors: Raju V V
authors: RV
authors: Tatituri
authors: Gerald F M
authors: GF
authors: Watts
authors: Veemal
authors: V
authors: Bhowruth
authors: Nathaniel
authors: N
authors: Barton
authors: Alissa
authors: A
authors: Rothchild
authors: Fong-Fu
authors: FF
authors: Hsu
authors: Catarina F
authors: CF
authors: Almeida
authors: Liam R
authors: LR
authors: Cox
authors: Lothar
authors: L
authors: Eggeling
authors: Susanna
authors: S
authors: Cardell
authors: Jamie
authors: J
authors: Rossjohn
authors: Dale I
authors: DI
authors: Godfrey
authors: Samuel M
authors: SM
authors: Behar
authors: Gurdyal S
authors: GS
authors: Besra
authors: Michael B
authors: MB
authors: Brenner
authors: Manfred
authors: M
authors: Brigl
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism; D000942:Antigens, Bacterial / Q000276:immunology* / Q000378:metabolism; D055610:Antigens, CD1d / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D002308:Cardiolipins / Q000276:immunology / Q000378:metabolism; D002460:Cell Line; D002478:Cells, Cultured; D048230:Corynebacterium glutamicum / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D005699:Galactosylceramides / Q000276:immunology / Q000378:metabolism; D006825:Hybridomas / Q000276:immunology / Q000378:metabolism; D008264:Macrophages / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009169:Mycobacterium tuberculosis / Q000276:immunology / Q000378:metabolism; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D055611:Natural Killer T-Cells / Q000276:immunology* / Q000378:metabolism; D010715:Phosphatidylglycerols / Q000276:immunology / Q000378:metabolism; D010743:Phospholipids / Q000276:immunology* / Q000378:metabolism; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology* / Q000378:metabolism; D051193:Toll-Like Receptors / Q000276:immunology / Q000378:metabolism; D017855:Transferases (Other Substituted Phosphate Groups) / Q000235:genetics / Q000276:immunology / Q000378:metabolism
chemical_list: D000942:Antigens, Bacterial; D055610:Antigens, CD1d; D001426:Bacterial Proteins; D002308:Cardiolipins; C526879:Cd1d1 protein, mouse; D005699:Galactosylceramides; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D010715:Phosphatidylglycerols; D010743:Phospholipids; D016693:Receptors, Antigen, T-Cell, alpha-beta; D051193:Toll-Like Receptors; C493154:alpha-galactosylceramide; D017855:Transferases (Other Substituted Phosphate Groups); C020676:CDP-diacylglycerol-glycerol-3-phosphate 3-phosphatidyltransferase