Ligand-receptor interactions of V-domain Ig-containing suppressor of T cell activation and programmed death-1 suppress the anticancer activities of T cells

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Background: V-domain immunoglobulin-containing suppressor of T cell activation (VISTA) is a unique multifunctional immune checkpoint protein, which can display both receptor and ligand properties. It plays a crucial role in the cancer immune evasion machinery operated by a wide range of human malignancies and may thus be considered as a potential target for immunotherapy of cancer. Receptors of VISTA through which this protein transmits immunosuppressive signals under various normal and pathological conditions remain to be identified. Materials and methods: To conduct the study, we used human recombinant proteins and various human cell lines as well as primary T cells. A wide range of techniques including tissue culture and co-cultures, Western blot analysis, on-cell Western, ELISA, co-immunoprecipitation, biochemical assays and synchrotron radiation circular dichroism spectroscopy were employed. Results: of ∼2.3 μM detected by synchrotron radiation circular dichroism spectroscopy. Conclusions: These results open a completely new chapter in our understanding of the concept of immune checkpoint proteins, where some of them clearly show both ligand and receptor activities and display multifunctional properties.