Reactivity | HuSpecies Glossary |
Applications | Bioactivity |
Format | Carrier-Free |
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 0.1-0.4 µg/mL when stimulated with 1 µg/mL Recombinant Human B7‑1/CD80 Fc Chimera (Catalog # 140-B1) in the presence of PHA. |
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Source | Spodoptera frugiperda, Sf 21 (baculovirus)-derived human CTLA-4 protein
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Accession # | |||||||||
N-terminal Sequence | Ala37 |
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Structure / Form | Disulfide-linked homodimer |
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Protein/Peptide Type | Recombinant Proteins |
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Gene | CTLA4 |
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Purity | >90%, by SDS-PAGE visualized with Silver Staining and quantitative densitometry by Coomassie® Blue Staining. |
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Endotoxin Note | <0.10 EU per 1 μg of the protein by the LAL method. |
Dilutions |
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Theoretical MW | 40 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. |
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Publications |
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Storage | Use a manual defrost freezer and avoid repeated freeze-thaw cycles.
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Buffer | Lyophilized from a 0.2 μm filtered solution in PBS. |
Purity | >90%, by SDS-PAGE visualized with Silver Staining and quantitative densitometry by Coomassie® Blue Staining. |
Reconstitution Instructions | Reconstitute at 200 μg/mL in sterile PBS. |
CTLA-4 (cytotoxic T-lymphocyte-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).
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