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NKG2A is a member of the C-type lectin superfamily of single-pass transmembrane Type II membrane glycoproteins, comprising an intracellular domain, a transmembrane domain, and an extracellular lectin-like domain. The intracellular domain contains two ITIMs (immunoreceptor tyrosine-based inhibitory motifs) that participate in inhibitory signal transduction. NKG2A serves as a critical immune checkpoint for natural killer (NK) cells and CD8+ T cells. NKG2A is expressed as a heterodimer with CD94—which also belongs to the C-type lectin superfamily—and the ligand for this NKG2A/CD94 heterodimeric receptor is a non-classical MHC Class I molecule. Upon binding, the NKG2A/CD94 complex transmits inhibitory signals to NK cells and CD8+ T cells; blocking NKG2A effectively unleashes the cytotoxic functions of these lymphocytes.

Binding of the NKG2A/CD94 receptor to the peptide-presenting molecule HLA-E leads to the phosphorylation of the ITIMs within NKG2A. These phosphorylated ITIMs are responsible for recruiting and activating the intracellular phosphatases SHP-1 and SHP-2, thereby inhibiting the activating signals generated by receptors such as the T-cell receptor (TCR) and NKG2D. In contrast to classical HLA molecules—which are often lost in tumor cells—the expression of HLA-E is frequently upregulated in tumors. The interaction between NKG2A and HLA-E contributes to tumor immune evasion, and NKG2A-mediated mechanisms are currently being leveraged to develop potential anti-tumor therapeutic strategies. Furthermore, disrupting the interaction between NKG2A and its ligand has been demonstrated to effectively enhance anti-tumor immune responses. The expression of NKG2A correlates with disease severity in patients with COVID-19. Additionally, NKG2A is implicated in the pathological processes of various other immune-mediated conditions, including autoimmune diseases, inflammatory disorders, parasitic infections, and transplant rejection. These findings suggest that NKG2A represents a novel therapeutic target for a wide range of immune-mediated diseases. Furthermore, increasing evidence indicates that NKG2A also plays a significant role in other immune-related diseases, including viral infections, autoimmune diseases, inflammatory diseases, parasitic infections, and transplant rejection.

The CHO-K1 Human HLA-E aAPC Cell Model—effectively simulates the signal transduction process of NKG2A &HLA-E *in vivo*. The underlying principle is illustrated in the figure below.

Figure 1. Schematic Diagram of the CHO-K1 Human HLA-E aAPC Cell (Adherent) Model

Figure 2. Dose Response of NKG2A Blocking Ab in NKG2A Effector Reporter Cell(C56) With HLA-E aAPC Cell.