VISTA (human, recombinant)

V-Domain immunoglobulin (Ig) suppressor of T cell activation (VISTA) is a type I transmembrane receptor and negative checkpoint regulator encoded by VSIR in humans.¹ It is composed of an N-terminal extracellular domain, containing a signaling sequence, Ig V domain, and stalk region, a transmembrane domain, and a cytoplasmic tail that contains a conserved Src homology 2 (SH2) binding motif. It is expressed in myeloid cells, monocytes, macrophages, dendritic cells, naïve CD4⁺ and FoxP3⁺ regulatory T cells, and natural killer (NK) cells.² VISTA arrests cell division and suppresses early T cell receptor activation when expressed on CD4⁺ T cells, and suppresses antigen-specific T cell activation when expressed on antigen presenting cells.³ Vsir^-/- mice are resistant to tumor induction compared with wild-type mice in a GL261 mouse glioma model.^2,3 Monocyte levels of VISTA are increased in patients with HIV compared with healthy controls.⁴ VSIR expression is increased in the circulating immune cells of patients with systemic lupus erythematosus (SLE) and in skin biopsies from patients with discoid lupus erythematosus (DLE). Cayman's VISTA (human, recombinant) protein consists of 173 amino acids, has a calculated molecular mass of 19.6 kDa, and a predicted N-terminus of Phe33 after signal peptide cleavage. By SDS-PAGE, under reducing conditions, the molecular mass of the protein is 38-42 kDa due to apparent post-translational modifications.

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1. Nowak, E.C., Lines, J.L., Varn, F.S., et al. Immunoregulatory functions of VISTA. Immunol. Rev. 276(1), 66-79 (2017).

2. ElTanbouly, M.A., Croteau, W., Noelle, R.J., et al. VISTA: A novel immunotherapy target for normalizing innate and adaptive immunity. Semin. Immunol. 42, 101308 (2019).

3. Ni, L., and Dong, C. New checkpoints in cancer immunotherapy. Immunol. Rev. 276(1), 52-65 (2017).

4. Wang, G., Tai, R., Wu, Y., et al. The expression and immunoregulation of immune checkpoint molecule VISTA in autoimmune diseases and cancers. Cytokine Growth Factor Rev. 52, 1-14 (2020).