Journal
NATURE COMMUNICATIONS
Volume 10, Issue -, Pages -Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41467-019-12941-9
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Funding
- National Health and Medical Research Council of Australia (NHMRC) [1013667, 1016629]
- Australian Research Council (ARC) [CE140100011, DP160100597]
- Fundacao para a Ciencia e a Tecnologia (FCT) [SFRH/BD/74906/2010]
- ARC [FT140100278, FT130100103, FT160100074]
- CSL Centernary Fellowship
- NHMRC [1117766]
- Australian ARC Laureate Fellowship
- National Health and Medical Research Council of Australia [1117766] Funding Source: NHMRC
- Fundação para a Ciência e a Tecnologia [SFRH/BD/74906/2010] Funding Source: FCT
- Australian Research Council [FT160100074, FT140100278] Funding Source: Australian Research Council
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Type I and type II natural killer T (NKT) cells are restricted to the lipid antigen-presenting molecule CD1d. While we have an understanding of the antigen reactivity and function of type I NKT cells, our knowledge of type II NKT cells in health and disease remains unclear. Here we describe a population of type II NKT cells that recognise and respond to the microbial antigen, a-glucuronosyl-diacylglycerol (alpha-GlcADAG) presented by CD1d, but not the prototypical type I NKT cell agonist, a-galactosylceramide. Surprisingly, the crystal structure of a type II NKT TCR-CD1d-alpha-GlcADAG complex reveals a CD1d F'-pocket-docking mode that contrasts sharply with the previously determined A'-roof positioning of a sulfatide-reactive type II NKT TCR. Our data also suggest that diverse type II NKT TCRs directed against distinct microbial or mammalian lipid antigens adopt multiple recognition strategies on CD1d, thereby maximising the potential for type II NKT cells to detect different lipid antigens.
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