Functions of NKG2D in CD8 + T cells: an opportunity for immunotherapy

• Published in: Cellular & molecular immunology Vol. 15; no. 5; pp. 470 - 479
• Main Authors: Prajapati, Kushal, Perez, Cynthia, Rojas, Lourdes Beatriz Plaza, Burke, Brianna, Guevara-Patino, Jose A
• Format: Journal Article
• Language: English
• Published: China Nature Publishing Group 01.05.2018; Nature Publishing Group UK
• Subjects: Autoimmunity; Cancer; CD28 antigen; CD8 antigen; Cell activation; Immunological memory; Immunotherapy; Lymphocytes; Lymphocytes T; Natural killer cells; NKG2 antigen; Receptor mechanisms; Review; T cell receptors; NKG2D; CD8+ T Cell; Auto-immunity; Immunotherapy; Memory; CD28; Immunity; Cancer
• ISSN: 1672-7681; 2042-0226
• DOI: 10.1038/cmi.2017.161

Natural killer group 2 member D (NKG2D) is a type II transmembrane receptor. NKG2D is present on NK cells in both mice and humans, whereas it is constitutively expressed on CD8 T cells in humans but only expressed upon T-cell activation in mice. NKG2D is a promiscuous receptor that recognizes stress-induced surface ligands. In NK cells, NKG2D signaling is sufficient to unleash the killing response; in CD8 T cells, this requires concurrent activation of the T-cell receptor (TCR). In this case, the function of NKG2D is to authenticate the recognition of a stressed target and enhance TCR signaling. CD28 has been established as an archetype provider of costimulation during T-cell priming. It has become apparent, however, that signals from other costimulatory receptors, such as NKG2D, are required for optimal T-cell function outside the priming phase. This review will focus on the similarities and differences between NKG2D and CD28; less well-described characteristics of NKG2D, such as the potential role of NKG2D in CD8 T-cell memory formation, cancer immunity and autoimmunity; and the opportunities for targeting NKG2D in immunotherapy.