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. Author manuscript; available in PMC: 2023 May 5.
Published in final edited form as: Annu Rev Immunol. 2022 Nov 29;41:17–38. doi: 10.1146/annurev-immunol-101921-044122

Figure 3.

Figure 3

Inhibitory receptors shared by T cells and NK cells. (a) The CD161 inhibitory receptor is expressed by NK cells, and its expression is highly upregulated by tumor-infiltrating CD8 and CD4 T cells. It binds to the CLEC2D ligand, which can be expressed by tumor cells and immune cells in the tumor microenvironment. CD161 signaling inhibits the cytotoxic activity of NK cells and CD8 T cells, and it also inhibits cytokine production by both lymphocyte populations. (b) The CD226 activating receptor is regulated by three inhibitory receptors in NK cells and T cells: TIGIT, CD96, and PVRIG. CD226 binds to CD155, a protein that is highly expressed in a number of human cancer types. TIGIT and CD96 bind to CD155 with a higher affinity compared to CD226, thus outcompeting the activating receptor for ligand binding. The primary ligand for the PVRIG inhibitory receptor is PVRL2. (c) The inhibitory NKG2A/CD94 receptor is expressed by NK cells and a subset of CD8 T cells. It binds HLA-E, whose expression is induced by IFN-γ secreted by activated T cells and NK cells. Abbreviation: APC, antigen-presenting cell.