CD1d ‐Restricted Natural Killer T Cells

Abstract

Natural killer T (NKT) cells that express the semi‐invariant T‐cell receptor are innate‐like lymphocytes whose functions are controlled by self and foreign glycolipid ligands. Such ligands are presented by the antigen‐presenting, MHC class I‐like molecule CD1d, which belongs to a family of lipid antigen‐presenting molecules collectively called CD1. Activation of NKT cells in vivo results in rapid release of copious amounts of effector cytokines and chemokines with which they regulate innate and adaptive immune responses to pathogens, certain types of cancers and self‐antigens. The nature of CD1d‐restricted ligands, the manners in which they are recognised and the unique effector functions of NKT cells suggest an immunoregulatory role for this T‐cell subset. Their ability to respond fast and our ability to steer NKT cell cytokine responses to altered lipid ligands make them an important target for vaccine design and immunotherapies against autoimmune diseases. This article summarises our current understanding of CD1d‐restricted NKT cell biology and how these innate‐like lymphocytes control inflammation. Key Concepts CD1d molecules belong to a family of lipid antigen‐presenting molecules collectively called CD1. CD1d molecules resemble peptide antigen‐presenting MHC class I molecules. CD1d molecules restrict the specificity and functions of Natural killer T (NKT) cells. NKT cells recognise self‐ and nonself‐lipid ligands. Antigen recognition quickly activates NKT cells, which respond immediately by releasing proinflammatory and immunoregulatory cytokines and chemokines. Activated NKT cells communicate with cells of the innate and adaptive immune systems by cell–cell interactions and/or via soluble mediators. Such communications allow NKT cells to control immune responses to microbial pathogens and certain cancers. NKT‐cell activation has beneficial and, sometimes, adverse effects on certain autoimmune and metabolic disorders. NKT cells are targets for vaccine adjuvants and immunotherapies.

Eliciting Epitope-Specific CD8+ T Cell Response by Immunization with Microbial Protein Antigens Formulated with α-Galactosylceramide: Theory, Practice, and Protocols

“…NKT cell licensing of DCs facilitates antigen cross presentation by a less well-understood mechanism(s) [42, 44, 65]. Together, this provides stimulus to naïve antigen-specific CD8 + T cell precursors that then proliferate and differentiate into effector and memory CD8 + T cells [45]…”

“…Hence, harnessing a non-polymorphic antigen-presenting molecule and invariant T cells as vaccine targets that can provide help can be a viable option for enhancing CD8 + T cell responses to subunit antigens. CD1d and the restricted semi-invariant natural killer T (NKT) cells have shown significant promise as experimental vaccine targets [44]; their biology has been recently reviewed elsewhere [45]. …”

“…Activated NKT cells and DCs together stimulate naïve antigen-specific CD8 + T cell precursors, which then proliferate and differentiate into effector and memory CD8 + T cells (Fig. 1; [28, 44, 45, 49, 50]). By virtue of its ability to communicate to virtually all cell types of the immune system, αGalCer has proven to be a potent adjuvant that enhances antibody and CD4 T cell responses to foreign antigens (reviewed in Ref.…”

“…By virtue of its ability to communicate to virtually all cell types of the immune system, αGalCer has proven to be a potent adjuvant that enhances antibody and CD4 T cell responses to foreign antigens (reviewed in Ref. [45]).…”

“…We recently demonstrated the potency of αGalCer as a CD8 + T cell adjuvant for in vivo immunogenicity and protection studies which exploited pathogen-derived protein antigens ([28] and unpublished data). It is noteworthy that the activation of NKT cells by αGalCer results in the production of proinflammatory as well as immunoregulatory cytokines and chemokines (reviewed in [45]). Since DC activation and licensing as well as CD8 + T cell differentiation require proinflammatory cytokines and chemokines, efforts to synthesize and identify αGalCer analogues that elicit proinflammatory activity are being sought but are not discussed here ( see Table 1; reviewed in Ref.…”