Recombinant Rat VISTA/B7-H5/PD-1H Fc Chimera Protein, CF Summary
Accession # NP_001037765.1
|Formulation||Lyophilized from a 0.2 μm filtered solution in PBS.|
|Reconstitution||Reconstitute at 200 μg/mL in PBS.|
|Shipping||The product is shipped at ambient temperature. Upon receipt, store it immediately at the temperature recommended below.|
|Stability & Storage:||
Recombinant Rat VISTA/B7-H5/PD-1H Fc Chimera (Catalog # 2288-B7) inhibits IFN-gammasecretion by human peripheral blood mononuclear cells in the presence ofanti-CD3 antibody. The ED50 for this effect is 1-6 μg/mL.
2 μg/lane of Recombinant Rat VISTA/B7-H5/PD-1H was resolved with SDS-PAGE underreducing (R) and non-reducing (NR) conditions and visualized by Coomassie® Bluestaining, showing bands at 60-70 kDa and 120-140 kDa, respectively.
V-domain Ig suppressor of T cell activation (VISTA), also known as platelet receptor Gi24, Dies1, SISP1, PD-1H, and B7‑H5, is a 50-60 kDa transmembrane glycoprotein with homology to B7-like immune co-stimulatory molecules (1, 2). Mature rat VISTA contains a 160 amino acid (aa) extracellular domain (ECD) with one Ig-like domain, a 24 aa transmembrane segment, and a 96 aa cytoplasmic domain. The ECD of rat VISTA shares a 78% and 67% aa sequence identity with mouse and human VISTA, respectively. In human VISTA, a 30 kDa ECD can be shed by MT1‑MMP, leaving a 25-30 kDa fragment remaining in the membrane (3). VISTA promotes both MT1‑MMP expression and the MT1-MMP mediated activation of MMP-2 (3). VISTA has been shown to support the differentiation of embryonic stem cells (ESC) and enhances BMP-4 induced signaling in ESC, but it is also down-regulated following BMP-4 exposure (4, 5). Vista can bind directly to BMP-4, but it also associates with the type I BMP receptor Activin RIB/ALK 4 (4, 5). VISTA is highly expressed on mature CD11b high myeloid-derived APCs and to a lesser extent on CD4+, CD8+, and T regs and is also found on tumor infiltrating lymphocytes (7). It is up-regulated in vivo on activated monocytes and dendritic cells (5). VISTA inhibits CD4+ and CD8+ T cell proliferation, and their production of IL2 and IFN-gamma (6). Its expression on tumor cells attenuates the antitumor immune response and enables more rapid tumor progression (6). Suppression of VISTA signaling was shown to increase the rate of progression in the mouse autoimmune disease model EAE (6). VISTA-Ig suppressed proliferation of T cells but not B cells and blunted the production of T cell cytokines and activation markers, suggesting that VISTA as a negative checkpoint regulator suppresses T cell activation (8, 9).
- Flajnik, M.F. et al. (2012) Immunogenetics 64:571.
- Wilcox, R.A. et al. (2012) Eur. J. Haematol. 88:465.
- Sakr, M.A. et al. (2010) Cancer Sci. 101:2368.
- Aloia, L. et al. (2010) J. Biol. Chem.285:7776.
- Parisi, S. et al. (2012) FASEB J. 26:3957.
- Wang, L. et al. (2011) J. Exp. Med. 208:577.
- Flies, D.B. et al. (2014) J Clin Invest. 124:1966.
- Lines, J.L. et al. (2014) Cancer Res. 74:1924.
- Nowak, E.C. et al. (2017) Immunol Rev. 276:66.
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