Recombinant Human CTLA-4 Fc Chimera (CHO-expressed), CF Summary
Details of Functionality
Measured by its ability to inhibit IL-2 secretion by stimulated Jurkat human acute T cell leukemia cells. Linsley, P.S. et al. (1991) J. Exp. Med. 174:561. The ED50 for this effect is 0.03-0.15 μg/mL when stimulated with 1 μg/mL Recombinant Human B7‑1/CD80 Fc Chimera (Catalog # 140-B1).
>95%, by SDS-PAGE under reducing conditions and visualized by silver stain
<0.01 EU per 1 μg of the protein by the LAL method.
40.1 kDa (monomer). Disclaimer note: The observed molecular weight of the protein may vary from the listed predicted molecular weight due to post translational modifications, post translation cleavages, relative charges, and other experimental factors.
53-58 kDa, reducing conditions
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ligand and transmembrane spliced cytotoxic T lymphocyte associated antigen 4
CTLA-4 (cytotoxic T-lymphocyte associated protein‑4, designated CD152), is a type I transmembrane T cell inhibitory molecule that is a member of the Ig superfamily (1, 2). Human or mouse CTLA-4 cDNA encodes 223 amino acids (aa) including a 35 aa signal sequence, a 126 aa extracellular domain (ECD) with one Ig-like V-type domain, a 21 aa transmembrane (TM) sequence, and a 41 aa cytoplasmic sequence. It is found as a covalent homodimer of 41-43 kDa (2) Within the ECD, human CTLA-4 shares 68%, 71% and 83‑86% aa sequence identity with mouse, rat and porcine/bovine/rabbit/feline/canine CTLA-4, respectively. A 174 aa form that lacks TM and cytoplasmic sequences (sCTLA-4) is possibly secreted (3-5). Isoforms of 56-79 aa that mainly contain parts of the cytoplasmic domain are reported. In mouse, an isoform lacking the Ig-like domain has ligand-independent inhibitory activity and is termed liCTLA-4 (6). CD28, which is structurally related to CTLA-4, is constitutively expressed on naïve T cells and promotes T cell activation when engaged by B7-2 on antigen-presenting cells (APC) within the immunological synapse (IS) (1, 7, 8). In contrast, CTLA-4 is recruited from intracellular vesicles to the IS beginning 1-2 days after T cell activation (2, 7, 8). It forms a linear lattice with B7-1 on APC, inducing negative regulatory signals and ending T cell activation (9). Abatacept, a therapeutic human CTLA-4-Ig fusion protein (trade name Orencia), competes with CD28 for B7-1 and B7-2 binding and has been used to antagonize T cell activation in autoimmune conditions and to enhance transplant survival (10). Mice deleted for CTLA-4 show no abnormalities until after birth, but then develop lethal autoimmune reactions due to continued T cell activation and poor control by regulatory T cells, which constitutively express CTLA-4 in wild-type mice and humans (11-13).
CD86 - I work in tandem with CD80 CD86 belongs to the immunoglobulin superfamily of proteins that drive innate and adaptive immune responses. It is an 80kD co-stimulatory molecule for the priming and activation of naive and memory T-cells, respectively. CD86 is expressed on activated... Read full blog post.
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