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Review
. 2017 Feb 1;198(3):1015-1021.
doi: 10.4049/jimmunol.1601399.

Type II NKT Cells and Their Emerging Role in Health and Disease

Madhav V Dhodapkar  1   2   3 , Vipin Kumar  4
Affiliations
Review

Type II NKT Cells and Their Emerging Role in Health and Disease

Madhav V Dhodapkar et al. J Immunol. .

Abstract

NKT cells recognize lipid Ags presented by a class I MHC-like molecule CD1d, a member of the CD1 family. Although most initial studies on NKT cells focused on a subset with semi-invariant TCR termed invariant NKT cells, the majority of CD1d-restricted lipid-reactive human T cells express diverse TCRs and are termed type II NKT cells. These cells constitute a distinct population of circulating and tissue-resident effector T cells with immune-regulatory properties. They react to a growing list of self- as well as non-self-lipid ligands, and share some properties with both invariant NKT and conventional T cells. An emerging body of evidence points to their role in the regulation of immunity to pathogens/tumors and in autoimmune/metabolic disorders. An improved understanding of the biology of these cells and the ability to manipulate their function may be of therapeutic benefit in diverse disease conditions.

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Figures

Figure 1
Figure 1
Antigenic targets for type II NKT cells. Sulfatide was the first and remains the best characterized ligand for type II NKT cells. More recently several other antigens including lysolipids such as lysophosphatidylcholine and Lyso-GL-1 have been shown to be recognized by type II NKT cells.
Figure 2
Figure 2
Differences in the mechanisms of TCR docking in CD1d-restricted lipid-reactive type I and II NKT cells and MHC I-restricted peptide-specific specific conventional T cells. Figure shows a top down view of the MHC-peptide or CD1d-lipid complex. Circles represent the orientation of the CDR3α and CDR3β region. In contrast to type I NKT cells, type II NKT sulfatide-reactive TCR uses the CDR3β to contact the antigen and docks in an anti-parallel fashion similar to the situation for conventional T cells.
Figure 3
Figure 3
Cross-talk between type II NKT cells and other immune cells including DCs, conventional T cells, B cells and type I NKT cells. An important role of type II NKT cells in the immune system may be their ability to interact with several other cell types to modulate their function. Most of these interactions have to date only been studied in the context of murine type II NKT cells and sulfatide-reactive T cells in particular.
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