PD-1 (Intracellular Domain) (D7D5W) Rabbit mAb

The programmed cell death 1 protein (PD-1, PDCD1, CD279) is a member of the CD28 family of immunoreceptors that regulate T cell activation and immune responses (1-3). The PD-1 protein contains an extracellular Ig V domain, a transmembrane domain, and a cytoplasmic tail that includes an immunoreceptor tyrosine-based inhibitory motif (ITIM) and an immunoreceptor tyrosine-based switch motif (ITSM). PD-1 is activated by the cell surface ligands PD-L1 and PD-L2 (4). Upon activation, PD-1 ITIM and ITSM phosphorylation leads to the recruitment of the protein tyrosine phosphatases SHP-1 and SHP-2, which suppress TCR signaling (5-7). In addition to activated T cells, PD-1 is expressed in activated B cells and monocytes, although its function in these cell types has not been fully characterized (8). The PD-1 pathway plays an important role in immune tolerance (3); however, research studies show that cancer cells often adopt this pathway to escape immune surveillance (9). Consequently, blockade of PD-1 and its ligands is proving to be a sound strategy for neoplastic intervention (10). 1.Ishida, Y. et al. (1992) EMBO J 11, 3887-95. 2.Shinohara, T. et al. (1994) Genomics 23, 704-6. 3.Nishimura, H. et al. (1999) Immunity 11, 141-51. 4.Freeman, G.J. et al. (2000) J Exp Med 192, 1027-34. 5.Yokosuka, T. et al. (2012) J Exp Med 209, 1201-17. 6.Sheppard, K.A. et al. (2004) FEBS Lett 574, 37-41. 7.Chemnitz, J.M. et al. (2004) J Immunol 173, 945-54. 8.Thibult, M.L. et al. (2013) Int Immunol 25, 129-37. 9.Dong, H. et al. (2002) Nat Med 8, 793-800. 10.Topalian, S.L. et al. (2012) Curr Opin Immunol 24, 207-12.