CTLA-4 (E2V1Z) Rabbit mAb

Cytotoxic T-lymphocyte protein 4 (CTLA-4, CD152) is an Ig superfamily member that negatively regulates early T cell activation (1-4). The CTLA-4 protein is primarily expressed on T cells, including CD8+ cytotoxic T cells, CD4+ helper T cells, and CD4+/FoxP3+ regulatory T cells (1,2). CTLA-4 protein competes with CD28 for B7.1 (CD80) and B7.2 (CD86) binding at the cell surface, which results in the downregulation of T cell activity (5). The activation of SHP-2 and PP2A downstream of CTLA-4 attenuates TCR signaling (6). Research studies indicate that CTLA4 knockout mice display lymphoproliferative disorders leading to early death, confirming the role of CTLA-4 as a negative regulator of T cells (7). Mutations in the corresponding CTLA4 gene are associated with multiple disorders, including insulin-dependent diabetes mellitus, Graves' disease, Hashimoto thyroiditis, celiac disease, systemic lupus erythematosus, and type V autoimmune lymphoproliferative syndrome (8,9). Additional studies demonstrate that CTLA-4 blockade is an effective strategy for tumor immunotherapy (10-12). 1.Brunet, J.F. et al. (1987) Nature 328, 267-70. 2.Brunet, J.F. et al. (1988) Immunol Rev 103, 21-36. 3.Dariavach, P. et al. (1988) Eur J Immunol 18, 1901-5. 4.Linsley, P.S. (1995) J Exp Med 182, 289-92. 5.Collins, A.V. et al. (2002) Immunity 17, 201-10. 6.Rudd, C.E. et al. (2009) Immunol Rev 229, 12-26. 7.Waterhouse, P. et al. (1995) Science 270, 985-8. 8.Romo-Tena, J. et al. (2013) Autoimmun Rev 12, 1171-6. 9.Wang, J. et al. (2014) PLoS One 9, e85982. 10.Egen, J.G. et al. (2002) Nat Immunol 3, 611-8. 11.Hodi, F.S. et al. (2003) Proc Natl Acad Sci U S A 100, 4712-7. 12.Pardoll, D.M. (2012) Nat Rev Cancer 12, 252-64.