Review

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

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Abstract

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.

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Author information

Affiliations

  1. Loyola University Chicago, Oncology Institute, Maywood, IL 60153, USA

    • Kushal Prajapati
    • , Cynthia Perez
    • , Lourdes Beatriz Plaza Rojas
    • , Brianna Burke
    •  & Jose A Guevara-Patino

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Competing interests

The authors declare no conflict of interest.

Corresponding author

Correspondence to Jose A Guevara-Patino.