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Type II NKT cells: a distinct CD1d-restricted immune regulatory NKT cell subset

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Abstract

Type II natural killer T cells (NKT) are a subset of the innate-like CD1d-restricted lymphocytes that are reactive to lipid antigens. Unlike the type I NKT cells, which express a semi-invariant TCR, type II NKT cells express a broader TCR repertoire. Additionally, other features, such as their predominance over type I cells in humans versus mice, the nature of their ligands, CD1d/lipid/TCR binding, and modulation of immune responses, distinguish type II NKT cells from type I NKT cells. Interestingly, it is the self-lipid-reactivity of type II NKT cells that has helped define their physiological role in health and in disease. The discovery of sulfatide as one of the major antigens for CD1d-restricted type II NKT cells in mice has been instrumental in the characterization of these cells, including the TCR repertoire, the crystal structure of the CD1d/lipid/TCR complex, and their function. Subsequently, several other glycolipids and phospholipids from both endogenous and microbial sources have been shown to activate type II NKT cells. The activation of a specific subset of type II NKT cells following administration with sulfatide or lysophosphatidylcholine (LPC) leads to engagement of a dominant immunoregulatory pathway associated with the inactivation of type I NKT cells, conventional dendritic cells, and inhibition of the proinflammatory Th1/Th17 cells. Thus, type II NKT cells have been shown to be immunosuppressive in autoimmune diseases, inflammatory liver diseases, and in cancer. Knowing their relatively higher prevalence in human than type I NKT cells, understanding their biology is imperative for health and disease.

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Acknowledgments

This work was supported by grants from the National Institutes of Health, USA, R01 CA100660 and R01 AA020864 (to VK). We thank the other members of the Kumar laboratory and Dr. Randle Ware for a critical reading of the manuscript.

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  1. Division of Gastroenterology, Department of Medicine, University of California San Diego, 9500 Gilman Drive, La Jolla, CA, 92037, USA

    Suryasarathi Dasgupta & Vipin Kumar

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  1. Suryasarathi Dasgupta
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Correspondence to Vipin Kumar.

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This article is published in the Special Issue CD1, MR1, NKT, and MAIT: Evolution and Origins of Non-peptidic Antigen Recognition by T lymphocytes with Guest Editor Dr. Dirk Zajonc

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Dasgupta, S., Kumar, V. Type II NKT cells: a distinct CD1d-restricted immune regulatory NKT cell subset. Immunogenetics 68, 665–676 (2016). https://doi.org/10.1007/s00251-016-0930-1

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