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iNKT cell autoreactivity: what is 'self' and how is it recognized?

Abstract

Following stimulation through their T cell receptor, invariant natural killer T (iNKT) cells function as innate effector cells by rapidly releasing large amounts of effector cytokines and chemokines and therefore have an important role in modulating the ensuing immune response. iNKT cells recognize, and are activated by, diverse glycolipid antigens, many of which are found in microorganisms. However, iNKT cells also show some reactivity to 'self'. Here, I outline our current understanding of iNKT cell autoreactivity and propose that several self lipids are probably involved in the positive selection and autoreactivity of iNKT cells.

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Figure 1: Mechanisms for triggering invariant natural killer T cell autoreactivity.
Figure 2: Structural overview of α-GalCer–CD1d recognition by the iNKT cell TCR.

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Acknowledgements

I thank members of my laboratory for discussions and P. Marrack, M. Kronenberg and D. Volker for critical reading of the manuscript. I apologize to colleagues whose works are relevant to iNKT cell autoreactivity but could not be cited owing to space constraints. I am supported by grants from the US National Institutes of Health and the Juvenile Diabetes Research Foundation.

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Gapin, L. iNKT cell autoreactivity: what is 'self' and how is it recognized?. Nat Rev Immunol 10, 272–277 (2010). https://doi.org/10.1038/nri2743

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