CTLA-4 Antibody (1003705) [Janelia Fluor® 549] Summary
                         
                                
                                
                                
            | Immunogen | Chinese Hamster Ovary cell line, CHO-derived human CTLA-4Ala37-Phe162
 Accession # P16410
 | 
            | Specificity | Detects human CTLA-4 in direct ELISAs. Detects human and moue CTLA-4 in Western blots. | 
            | Isotype | IgG1 | 
            | Clonality | Monoclonal | 
            | Host | Mouse | 
            | Purity | Protein A or G purified from hybridoma culture supernatant | 
            | Innovator's Reward | Test in a species/application not listed above to receive a full credit towards a future purchase. | 
                                
                          Applications/Dilutions
                                
                                    
                                    
                                        
                              
                                  | Dilutions | Agonist Activity Western Blot 
 | 
            | Application Notes | Optimal dilution of this antibody should be experimentally determined. | 
                                    
                                  Packaging, Storage & Formulations
            | Storage | Store at 4C in the dark. | 
            | Buffer | 50mM Sodium Borate | 
            | Preservative | 0.05% Sodium Azide | 
            | Purity | Protein A or G purified from hybridoma culture supernatant | 
Notes
                    
                        
Sold under license from the Howard Hughes Medical Institute, Janelia Research Campus.
                     Alternate Names for CTLA-4 Antibody (1003705) [Janelia Fluor® 549]
                     Background
 
                    
                    Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4), also known as CD152, is a cell surface glycoprotein belonging to the immunoglobulin family with a role in regulation of T cell activation (1). Human CTLA-4 is a 223 amino acid (aa) protein with a theoretical molecular weight of 24.6 kDa containing a leader peptide, a IgV-like domain, a transmembrane domain, and a cytoplasmic tail (1,2). CTLA-4 is both structurally and functionally related with another member of the immunoglobulin-related receptor family, CD28 (1-3). CTLA-4 and CD28 receptors are both expressed by CD4+ and CD8+ T cells and share two common ligands, CD80 (B7.1) and CD86 (B7.2), expressed on the surface of antigen presenting cells (APCs) (2,3). While CD28 is present on the plasma membrane of T cells, CTLA-4 is predominantly expressed intracellularly on vesicles in FoxP3+ regulatory T (Treg) cells and activated T cells due to endocytosis (3). While they share ligands, the two receptors have opposing functions in T cell activation; CD28 is involved in activation of T cells, while CTLA-4 functions as a negative regulator of T cell response (2,3). One of the primary functions of CTLA-4 is preventing autoimmunity (1-4). 
Similar to programmed cell death protein 1 (PD-1), CTLA-4 is an inhibitory immune checkpoint protein (3,5). Checkpoint blockade immunotherapy using drugs or antibodies to target CTLA-4 is one of the main approaches for cancer treatment (5). A number of drugs targeting CTLA-4, or a combination of CTLA-4/PD-1, have been approved for treatment of various cancers like melanoma, renal cell carcinoma, and colorectal cancer (5). While blocking CTLA-4 in the tumor microenvironment is a promising cancer therapeutic, the absence of CTLA-4 under normal conditions can have deleterious effects. Studies have found that patients with CTLA-4 deficiency or mutations have clinical features associated with autoimmunity and immune dysregulation (4). Treatment options for CTLA-4 deficiency includes immunoglobulin-replacement therapy, corticosteroids, CTLA-4-immunoglobulin (Ig) fusion protein, and, in life-threatening cases, hematopoietic stem cell transplantation (4,6). Additionally, engaging CD80/CD86 with CTLA-4-Ig is a common immunosuppressive treatment for rheumatoid arthritis and kidney transplant recipients (6). 
References
1. Romo-Tena, J., Gomez-Martin, D., & Alcocer-Varela, J. (2013). CTLA-4 and autoimmunity: new insights into the dual regulator of tolerance. Autoimmunity reviews, 12(12), 1171-1176. https://doi.org/10.1016/j.autrev.2013.07.002
2. Hosseini, A., Gharibi, T., Marofi, F., Babaloo, Z., & Baradaran, B. (2020). CTLA-4: From mechanism to autoimmune therapy. International immunopharmacology, 80, 106221. https://doi.org/10.1016/j.intimp.2020.106221
3. Rowshanravan, B., Halliday, N., & Sansom, D. M. (2018). CTLA-4: a moving target in immunotherapy. Blood, 131(1), 58-67. https://doi.org/10.1182/blood-2017-06-741033
4. Verma, N., Burns, S. O., Walker, L., & Sansom, D. M. (2017). Immune deficiency and autoimmunity in patients with CTLA-4 (CD152) mutations. Clinical and experimental immunology, 190(1), 1-7. https://doi.org/10.1111/cei.12997
5. Rotte A. (2019). Combination of CTLA-4 and PD-1 blockers for treatment of cancer. Journal of experimental & clinical cancer research : CR, 38(1), 255. https://doi.org/10.1186/s13046-019-1259-z
6. Bluestone, J. A., St Clair, E. W., & Turka, L. A. (2006). CTLA4Ig: bridging the basic immunology with clinical application. Immunity, 24(3), 233-238. https://doi.org/10.1016/j.immuni.2006.03.001
                      Limitations
 
                    
                    This product is for research use only and is not approved for use in humans or in clinical diagnosis. Primary Antibodies are 
guaranteed for 1 year from date of receipt.
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