CD1d-Restricted Type II NKT Cells Reactive With Endogenous Hydrophobic Peptides

Abstract

NKT cells belong to a distinct subset of T cells that recognize hydrophobic antigens presented by major histocompatibility complex class I-like molecules, such as CD1d. Because NKT cells stimulated by antigens can activate or suppress other immunocompetent cells through an immediate production of a large amount of cytokines, they are regarded as immunological modulators. CD1d-restricted NKT cells are classified into two subsets, namely, type I and type II. CD1d-restricted type I NKT cells express invariant T cell receptors (TCRs) and react with lipid antigens, including the marine sponge-derived glycolipid α-galactosylceramide. On the contrary, CD1d-restricted type II NKT cells recognize a wide variety of antigens, including glycolipids, phospholipids, and hydrophobic peptides, by their diverse TCRs. In this review, we focus particularly on CD1d-restricted type II NKT cells that recognize endogenous hydrophobic peptides presented by CD1d. Previous studies have demonstrated that CD1d-restricted type I NKT cells usually act as pro-inflammatory cells but sometimes behave as anti-inflammatory cells. It has been also demonstrated that CD1d-restricted type II NKT cells play opposite roles to CD1d-restricted type I NKT cells; thus, they function as anti-inflammatory or pro-inflammatory cells depending on the situation. In line with this, CD1d-restricted type II NKT cells that recognize type II collagen peptide have been demonstrated to act as anti-inflammatory cells in diverse inflammation-induction models in mice, whereas pro-inflammatory CD1d-restricted type II NKT cells reactive with sterol carrier protein 2 peptide have been demonstrated to be involved in the development of small vessel vasculitis in rats.

Keywords: CD1d; NKT cell; glycolipid; hydrophobic peptide; sulfatide.

Figure 1

Hypothetical diverse roles of CD1d-restricted type II NKT cells that recognize endogenous hydrophobic peptides. (A) Preceding inflammation sometimes results in the injury of own tissues. Under such situation, injured cells then present hydrophobic autoantigens, probably peptides, on their CD1d to activate CD1d-restricted type II NKT cells. Thereafter, activated CD1d-restricted type II NKT cells function to diminish inflammation by producing anti-inflammatory cytokines and by inducing apoptosis of effector cells via Fas/FasL interaction. (B) When CD1d-restricted type II NKT cells activated by endogenous hydrophobic peptides produce pro-inflammatory cytokines, the inflammation is exacerbated.