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

CD1d-restricted natural killer T (NKT) cells include two major subgroups. The most widely studied are V[alpha]14J[alpha][18.sup.+] invariant NKT (iNKT) cells that recognize the prototypical [alpha]-galactosylceramide antigen, whereas the other major group uses diverse T-cell receptor (TCR) [alpha]-a... Full description

Journal Title: Proceedings of the National Academy of Sciences of the United States of America January 29, 2013, Vol.110(5), pp.1827-1832
Main Author: Tatituri, Raju V V
Other Authors: Watts, Gerald F M , Bhowruth, Veemal , Barton, Nathaniel , Rothchild, Alissa , Hsu, Fong-Fu , Almeida, Catarina F , Cox, Liam R , Eggeling, Lothar , Cardell, Susanna , Rossjohn, Jamie , Godfrey, Dale I , Behar, Samuel M , Besra, Gurdyal S , Brenner, Michael B , Brigl, Manfred
Format: Electronic Article Electronic Article
Language: English
Subjects:
ID: E-ISSN: 1091-6490 ; DOI: 10.1073/pnas.1220601110
Link: http://search.proquest.com/docview/1283267852/?pq-origsite=primo
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title: Recognition of microbial and mammalian phospholipid antigens by NKT cells with diverse TCRs.
format: Article
creator:
  • Tatituri, Raju V V
  • Watts, Gerald F M
  • Bhowruth, Veemal
  • Barton, Nathaniel
  • Rothchild, Alissa
  • Hsu, Fong-Fu
  • Almeida, Catarina F
  • Cox, Liam R
  • Eggeling, Lothar
  • Cardell, Susanna
  • Rossjohn, Jamie
  • Godfrey, Dale I
  • Behar, Samuel M
  • Besra, Gurdyal S
  • Brenner, Michael B
  • Brigl, Manfred
subjects:
  • Animals–Immunology
  • Antigen-Presenting Cells–Metabolism
  • Antigens, Bacterial–Immunology
  • Antigens, Cd1d–Metabolism
  • Bacterial Proteins–Genetics
  • Cardiolipins–Immunology
  • Cell Line–Metabolism
  • Cells, Cultured–Genetics
  • Corynebacterium Glutamicum–Immunology
  • Galactosylceramides–Metabolism
  • Hybridomas–Immunology
  • Macrophages–Metabolism
  • Mice–Genetics
  • Mice, Inbred C57bl–Immunology
  • Mice, Knockout–Metabolism
  • Mycobacterium Tuberculosis–Immunology
  • Myeloid Differentiation Factor 88–Metabolism
  • Natural Killer T-Cells–Immunology
  • Phosphatidylglycerols–Metabolism
  • Phospholipids–Immunology
  • Receptors, Antigen, T-Cell, Alpha-Beta–Metabolism
  • Toll-Like Receptors–Microbiology
  • Transferases (Other Substituted Phosphate Groups)–Immunology
  • Transferases (Other Substituted Phosphate Groups)–Metabolism
  • Transferases (Other Substituted Phosphate Groups)–Genetics
  • Transferases (Other Substituted Phosphate Groups)–Immunology
  • Transferases (Other Substituted Phosphate Groups)–Metabolism
  • Transferases (Other Substituted Phosphate Groups)–Immunology
  • Transferases (Other Substituted Phosphate Groups)–Metabolism
  • Transferases (Other Substituted Phosphate Groups)–Immunology
  • Transferases (Other Substituted Phosphate Groups)–Metabolism
  • Transferases (Other Substituted Phosphate Groups)–Immunology
  • Transferases (Other Substituted Phosphate Groups)–Metabolism
  • Transferases (Other Substituted Phosphate Groups)–Immunology
  • Transferases (Other Substituted Phosphate Groups)–Metabolism
  • Transferases (Other Substituted Phosphate Groups)–Immunology
  • Transferases (Other Substituted Phosphate Groups)–Metabolism
  • Transferases (Other Substituted Phosphate Groups)–Genetics
  • Transferases (Other Substituted Phosphate Groups)–Immunology
  • Transferases (Other Substituted Phosphate Groups)–Metabolism
  • Antigens, Bacterial
  • Antigens, Cd1d
  • Bacterial Proteins
  • Cardiolipins
  • Cd1d1 Protein, Mouse
  • Galactosylceramides
  • Myd88 Protein, Mouse
  • Myeloid Differentiation Factor 88
  • Phosphatidylglycerols
  • Phospholipids
  • Receptors, Antigen, T-Cell, Alpha-Beta
  • Toll-Like Receptors
  • Alpha-Galactosylceramide
  • Transferases (Other Substituted Phosphate Groups)
  • Cdp-Diacylglycerol-Glycerol-3-Phosphate 3-Phosphatidyltransferase
ispartof: Proceedings of the National Academy of Sciences of the United States of America, January 29, 2013, Vol.110(5), pp.1827-1832
description: CD1d-restricted natural killer T (NKT) cells include two major subgroups. The most widely studied are V[alpha]14J[alpha][18.sup.+] invariant NKT (iNKT) cells that recognize the prototypical [alpha]-galactosylceramide antigen, whereas the other major group uses diverse T-cell receptor (TCR) [alpha]-and [beta]-chains, does not recognize [alpha]-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. type II natural killer cell | CD1 antigen presentation | innate immunity | adaptive immunity www.pnas.org/cgi/doi/10.1073/pnas.1220601110
language: eng
source:
identifier: E-ISSN: 1091-6490 ; DOI: 10.1073/pnas.1220601110
fulltext: fulltext
issn:
  • 10916490
  • 1091-6490
url: Link


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titleRecognition of microbial and mammalian phospholipid antigens by NKT cells with diverse TCRs.
creatorTatituri, Raju V V ; Watts, Gerald F M ; Bhowruth, Veemal ; Barton, Nathaniel ; Rothchild, Alissa ; Hsu, Fong-Fu ; Almeida, Catarina F ; Cox, Liam R ; Eggeling, Lothar ; Cardell, Susanna ; Rossjohn, Jamie ; Godfrey, Dale I ; Behar, Samuel M ; Besra, Gurdyal S ; Brenner, Michael B ; Brigl, Manfred
contributorTatituri, Raju V V (correspondence author) ; Tatituri, Raju V V (record owner)
ispartofProceedings of the National Academy of Sciences of the United States of America, January 29, 2013, Vol.110(5), pp.1827-1832
identifierE-ISSN: 1091-6490 ; DOI: 10.1073/pnas.1220601110
subjectAnimals–Immunology ; Antigen-Presenting Cells–Metabolism ; Antigens, Bacterial–Immunology ; Antigens, Cd1d–Metabolism ; Bacterial Proteins–Genetics ; Cardiolipins–Immunology ; Cell Line–Metabolism ; Cells, Cultured–Genetics ; Corynebacterium Glutamicum–Immunology ; Galactosylceramides–Metabolism ; Hybridomas–Immunology ; Macrophages–Metabolism ; Mice–Genetics ; Mice, Inbred C57bl–Immunology ; Mice, Knockout–Metabolism ; Mycobacterium Tuberculosis–Immunology ; Myeloid Differentiation Factor 88–Metabolism ; Natural Killer T-Cells–Immunology ; Phosphatidylglycerols–Metabolism ; Phospholipids–Immunology ; Receptors, Antigen, T-Cell, Alpha-Beta–Metabolism ; Toll-Like Receptors–Microbiology ; Transferases (Other Substituted Phosphate Groups)–Immunology ; Transferases (Other Substituted Phosphate Groups)–Metabolism ; Transferases (Other Substituted Phosphate Groups)–Genetics ; Transferases (Other Substituted Phosphate Groups)–Immunology ; Transferases (Other Substituted Phosphate Groups)–Metabolism ; Transferases (Other Substituted Phosphate Groups)–Immunology ; Transferases (Other Substituted Phosphate Groups)–Metabolism ; Transferases (Other Substituted Phosphate Groups)–Immunology ; Transferases (Other Substituted Phosphate Groups)–Metabolism ; Transferases (Other Substituted Phosphate Groups)–Immunology ; Transferases (Other Substituted Phosphate Groups)–Metabolism ; Transferases (Other Substituted Phosphate Groups)–Immunology ; Transferases (Other Substituted Phosphate Groups)–Metabolism ; Transferases (Other Substituted Phosphate Groups)–Immunology ; Transferases (Other Substituted Phosphate Groups)–Metabolism ; Transferases (Other Substituted Phosphate Groups)–Genetics ; Transferases (Other Substituted Phosphate Groups)–Immunology ; Transferases (Other Substituted Phosphate Groups)–Metabolism ; Antigens, Bacterial ; Antigens, Cd1d ; Bacterial Proteins ; Cardiolipins ; Cd1d1 Protein, Mouse ; Galactosylceramides ; Myd88 Protein, Mouse ; Myeloid Differentiation Factor 88 ; Phosphatidylglycerols ; Phospholipids ; Receptors, Antigen, T-Cell, Alpha-Beta ; Toll-Like Receptors ; Alpha-Galactosylceramide ; Transferases (Other Substituted Phosphate Groups) ; Cdp-Diacylglycerol-Glycerol-3-Phosphate 3-Phosphatidyltransferase
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descriptionCD1d-restricted natural killer T (NKT) cells include two major subgroups. The most widely studied are V[alpha]14J[alpha][18.sup.+] invariant NKT (iNKT) cells that recognize the prototypical [alpha]-galactosylceramide antigen, whereas the other major group uses diverse T-cell receptor (TCR) [alpha]-and [beta]-chains, does not recognize [alpha]-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. type II natural killer cell | CD1 antigen presentation | innate immunity | adaptive immunity www.pnas.org/cgi/doi/10.1073/pnas.1220601110
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titleRecognition of microbial and mammalian phospholipid antigens by NKT cells with diverse TCRs.
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titleRecognition of microbial and mammalian phospholipid antigens by NKT cells with diverse TCRs.
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