VSIR, also called V-domain Ig suppressor of T cell activation (VISTA) is a type I transmembrane protein that functions as an immune checkpoint and is encoded by the C10orf54 gene. VISTA is approximately 50kDa and belongs to the immunoglobulin superfamily and has one IgV domain. VSIR is part of the B7 family, is primarily expressed in white blood cells and its transcription is partially controlled by p53. There is evidence that VSIR can act as both a ligand and a receptor on T cells to inhibit T cell effector function and maintain peripheral tolerance. VSIR is produced at high levels in tumor-infiltrating lymphocytes, such as myeloid-derived suppressor cells and regulatory T cells, and its blockade with an antibody results in delayed tumor growth in mouse models of melanoma and squamous cell carcinoma.
mRNA expression analysis
Strain specific analysis of VSIR gene expression in WT and hVSIR mice by RT-PCR. Mouse vsir mRNA was detectable in bone marrow cell of wild-type (+/+) mice and heterozygous (H/+) mice. Human VSIR mRNA was detectable only in H/+, but not in +/+ mice.
Protein expression analysis
Strain specific VSIR expression analysis in homozygous B-hVSIR mice by flow cytometry. Bone marrow and blood were collected from WT and homozygous B-hVSIR (H/H) mice in vivo, and analyzed by flow cytometry with species-specific anti-VSIR antibody. Mouse VSIR was detectable in WT mice. Human VSIR was exclusively detectable in homozygous B-hVSIR but not WT mice.