The CD94/NKG2 Family of Receptors: From Molecules and Cells to Clinical Relevance

Abstract

Immune responses must be tightly regulated to avoid hyporesponsiveness on one hand or excessive inflammation and the development of autoimmunity (hyperresponsiveness) on the other hand. This balance is attained through the throttling of activating signals by inhibitory signals that ideally leads to an adequate immune response against an invader without excessive and extended inflammatory signals that promote the development of autoimmunity. The CD94/NKG2 family of receptors is composed of members with activating or inhibitory potential. These receptors are expressed predominantly on NK cells and a subset of CD8+ T cells, and they have been shown to play an important role in regulating responses against infected and tumorigenic cells. In this review, we discuss the current knowledge about this family of receptors, including ligand and receptor interaction, signaling, membrane dynamics, regulation of gene expression and their roles in disease regulation, infections, and cancer, and bone marrow transplantation.

A cross-sectional study of C-type lectin receptors (CD94 and CD314) in patients with HIV/AIDS and cancer

“…Our results agree with the literature regarding its constitutive expression in NK [43]. The values obtained from our group from healthy donors showed consistent with study of Almeida Oliveira et al (2011) whereas NK populations (and its subtypes), and NKT lymphocytes.…”

“…The CD94 receptor is normally expressed on the cell surface of most of the NK cell, TCRαβCD8+ lymphocytes and memory TCR γδ [43]. This can be expressed as a homodimer (CD94/CD94) having no involvement in the transmission of signals or as a heterodimer with members of the NKG2 family (eg, CD94/NKG2A) [7].…”

Binding Affinities of NKG2D and CD94 to Sialyl Lewis X-Expressing <i>N</i>-Glycans and Heparin

“…Inhibitory receptors NKG2A and B have two immunoreceptor tyrosine-based inhibitory motifs (ITIMs) in their cytoplasmic domains, while activating receptors NKG2C, E, and H have a positively charged residues within their transmembrane regions and associate with the immunoreceptor tyrosine-based activating motif (ITAM)-containing 12 kDa adaptor molecule DNAX-activating protein (DAP12). [2][3][4][5] The activating receptor NKG2D homodimer forms a salt-bridged hexamer with two homodimers of the YINM motif-containing adaptor molecule DAP-10 in humans 6) and recognizes several major histocompatibility complex (MHC) class I related ligands, such as MHC class I related chain family proteins (MIC) A/B 7) and the UL 16-binding proteins (ULBPs) 1-4 8) in humans. The C-type lectin-like receptors CD94 and NKG2D lack most of the conserved Ca 2ϩ -binding residues, 9,10) and the glycan ligands for NKG2D homodimer and CD94/NKG2s heterodimers have yet to be resolved.…”

Polymorphisms within the human leucocyte antigen-E gene and their associations with susceptibility to rheumatoid arthritis as well as clinical outcome of anti-tumour necrosis factor therapy

“…1 T lymphocytes [10,11]. The interaction between these receptors and HLA-E induces a cascade of competing activating and inhibitory signals, resulting in a modulation of NK and T lymphocytes function [12].…”