The V-domain Ig suppressor of T cell activation (VISTA) also known as PD-1 homolog (PD-1H) has recently been identified by our group and others as a novel NCR in the IgSF. VISTA is a type I transmembrane protein with a single IgV domain with sequence homology to the IgV domains of the members of CD28 and B7 families. VISTA cytoplasmic tail domain contains two potential protein kinase C binding sites as well as proline residues that could function as docking sites, suggesting that VISTA could potentially function as both a receptor and a ligand. VISTA does not contain ITIM-like motifs. Modeling algorithms have suggested homology to either PD-1 or PD-L1. The counter structures interacting with VISTA have not been identified yet.
Unlike PD-L1, VISTA expression is restricted to the hematopoietic compartment. It is constitutively and highly expressed on CD11b myeloid cells such as neutrophils, monocytes, macrophages, and DCs, and expressed at lower levels on naïve CD4 and CD8 T cells and Tregs both in humans and mice