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

Journal article
Authors R. V. V. Tatituri
G. F. M. Watts
V. Bhowruth
N. Barton
A. Rothchild
F. F. Hsu
C. F. Almeida
L. R. Cox
L. Eggeling
Susanna Cardell
J. Rossjohn
D. I. Godfrey
S. M. Behar
G. S. Besra
M. B. Brenner
M. Brigl
Published in Proceedings of the National Academy of Science of the United States of America
Volume 110
Issue 5
Pages 1827-1832
ISSN 0027-8424
Publication year 2013
Published at Institute of Biomedicine, Department of Microbiology and Immunology
Pages 1827-1832
Language en
Links dx.doi.org/10.1073/pnas.1220601110
Keywords type II natural killer T cell, CD1 antigen presentation, innate immunity, adaptive immunity, killer t-cells, innate-like, receptor, cd1, repertoire, sulfatide, distinct, glycolipids, population, activation, Kawakami, KazuyoshiKawakami, KNizet, VictorNizet, VBesra, Gurdyal S.Besra, GSTsuji, MoriyaTsuji
Subject categories Microbiology in the medical area

Abstract

CD1d-restricted natural killer T (NKT) cells include two major subgroups. The most widely studied are V alpha 14J alpha 18(+) 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.

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