Research Paper Volume 16, Issue 15 pp 11683—11728

Figure 1. Interactions between frontier immune checkpoint receptors and corresponding ligands. PD-1 is a potent T cell inhibitory receptor that binds to PDL1 or PDL2 to inhibit T cell activation, differentiation, and proliferation, resulting in an immunotolerant state; CTLA-4 has a significant strong affinity for CD80 and CD86, leading to blockade of CD80 and CD86 co-stimulation and inhibition of sustained T cell activation; Cell 1 (Th1) apoptosis, resulting in reduced autoimmune and anti-tumor immune responses. T cell immune receptors with TIGIT are thought to activate inhibitory receptors in T cells, NK cells, and regulatory T cells (Tregs), including NECTIN2 and high-affinity homologous receptor PVRs. CD160 binds broadly but weakly to MHC class I molecules, binds strongly to HVEM to attenuate the activity of specific subsets of CD4 T lymphocytes or enhance the activity of CD8 T cells, and also controls cytokine production in NK cells, while BTLA has two immunoreceptor tyrosine-based inhibitory motifs, and binding to HVEM is involved in providing an overall inhibitory immune response. CD200 is a type 1 cell membrane glycoprotein of the immunoglobulin supergene family, and its interaction with its receptor CD200R leads to the attenuation of multiple immune responses, FGL1, as a novel checkpoint ligand that surpasses the LAG3 classical ligand MHC II, is a proliferation and metabolism-related protein secreted by the liver, and their binding transmits negative signals to activated T cells to prevent immune-mediated tissue damage, and LAIR-1, a novel immunosuppressive transmembrane protein. Interactions with several of its ligands (e.g., extracellular matrix collagen, C1q complement components, surfactant protein D, and adiponectin) induce phosphorylation of ITIM and inhibit immune cell activation or differentiation, while LILRB4 binds to ligands such as ALCAM, ApoE, fibronectin, Galectin-8 and others to inhibit antigen-presenting cell activation, leading to immune tolerance.