The ins and outs of type I iNKT cell development

Mol Immunol. 2019 Jan:105:116-130. doi: 10.1016/j.molimm.2018.09.023. Epub 2018 Nov 28.

Abstract

Natural killer T (NKT) cells are innate-like lymphocytes that bridge the gap between the innate and adaptive immune responses. Like innate immune cells, they have a mature, effector phenotype that allows them to rapidly respond to threats, compared to adaptive cells. NKT cells express T cell receptors (TCRs) like conventional T cells, but instead of responding to peptide antigen presented by MHC class I or II, NKT cell TCRs recognize glycolipid antigen in the context of CD1d. NKT cells are subdivided into classes based on their TCR and antigen reactivity. This review will focus on type I iNKT cells that express a semi invariant Vα14Jα18 TCR and respond to the canonical glycolipid antigen, α-galactosylceramide. The innate-like effector functions of these cells combined with their T cell identity make their developmental path quite unique. In addition to the extrinsic factors that affect iNKT cell development such as lipid:CD1d complexes, co-stimulation, and cytokines, this review will provide a comprehensive delineation of the cell intrinsic factors that impact iNKT cell development, differentiation, and effector functions - including TCR rearrangement, survival and metabolism signaling, transcription factor expression, and gene regulation.

Keywords: CD1d; Innate lymphocytes; NKT cells; Natural killer T; T cell development; iNKT.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Antigen Presentation*
  • Antigens, CD1d / immunology*
  • Cytokines / immunology
  • Gene Expression Regulation / immunology
  • Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor / immunology
  • Glycolipids / immunology*
  • Histocompatibility Antigens Class I / immunology*
  • Humans
  • Natural Killer T-Cells / cytology
  • Natural Killer T-Cells / immunology*
  • Receptors, Antigen, T-Cell, alpha-beta / immunology*
  • Transcription, Genetic / immunology

Substances

  • Antigens, CD1d
  • CD1D protein, human
  • Cytokines
  • Glycolipids
  • Histocompatibility Antigens Class I
  • Receptors, Antigen, T-Cell, alpha-beta