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Review
. 2022 Aug 10:13:960852.
doi: 10.3389/fimmu.2022.960852. eCollection 2022.

Implications of NKG2A in immunity and immune-mediated diseases

Xiaotong Wang  1   2 , Huabao Xiong  1   2 , Zhaochen Ning  1   2
Affiliations
Review

Implications of NKG2A in immunity and immune-mediated diseases

Xiaotong Wang et al. Front Immunol. .

Abstract

In recent studies, NKG2A is revealed to be a key immune checkpoint for both natural killer (NK) cells and CD8+ T cells. It form heterodimer receptors with CD94, and targets the peptide-presenting human leukocyte antigen-E (HLA-E) molecules. Upon crosslinking, NKG2A/CD94 delivers inhibitory signals for NK cells and CD8+ T cells, while blocking NKG2A can effectively unleash functions of these cytotoxic lymphocytes. The interaction between NKG2A and HLA-E contributes to tumor immune escape, and NKG2A-mediated mechanisms are currently being exploited to develop potential antitumor therapeutic strategies. In addition, growing evidence shows that NKG2A also plays important roles in other immune-related diseases including viral infections, autoimmune diseases, inflammatory diseases, parasite infections and transplant rejection. Therefore, the current work focuses on describing the effect of NKG2A on immune regulation and exploring its potential role in immune-mediated disorders.

Keywords: HLA-E; NKG2A; autoimmune diseases; cancer immunotherapy; viral infections.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
NKG2A/CD94 and NKG2C/CD94 signalings in NK cells and T cells. HLA-E can bind to both NKG2A/CD94 and NKG2C/CD94 receptors. The interaction of NKG2A/CD94 receptor with peptide-presenting HLA­E results in the phosphorylation of ITIMs. Phosphorylated ITIMs are responsible for recruiting and activating intracellular phosphatase SHP-1/2, thus delivering negative signals. CD94/NKG2C heterodimers associates with DAP12 containing immune receptor tyrosine activating motifs (ITAMs), thus activating zeta-chain-associated protein kinase 70 kDa (ZAP70) and delivering activating signals.
See this image and copyright information in PMC

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