Programmed cell death protein 1 (CD279/PD-1) is a ~31 kDa protein. Inhibitory receptor on antigen activated T-cells that plays a critical role in induction and maintenance of immune tolerance to self. Delivers inhibitory signals upon binding to ligands, such as CD274/PDCD1L1 and CD273/PDCD1LG2. Following T-cell receptor (TCR) engagement, PDCD1 associates with TCR-CD3 in the immunological synapse and directly inhibits T-cell activation. Suppresses T-cell activation through the recruitment of PTPN11/SHP-2: following ligand-binding, PDCD1 is phosphorylated within the ITSM motif, leading to the recruitment of the protein tyrosine phosphatase PTPN11/SHP-2 that mediates dephosphorylation of key TCR proximal signaling molecules, such as ZAP70, PRKCQ/PKCtheta and CD247/CD3zeta. The PDCD1-mediated inhibitory pathway is exploited by tumors to attenuate anti-tumor immunity and facilitate tumor survival. CD279 is the therapeutic target of pembrolizumab (Keytruda) and nivolumab (Opdivo). 2. Nishimura, H. et al. (2001) Science (New York, N.Y.) 291, 319-22. PMID: 112090853. Okazaki, T. et al. (2001) Proceedings of the National Academy of Sciences of the United States of America 98, 13866-71. PMID: 116986464. Okazaki, T. et al. (2011) The Journal of experimental medicine 208, 395-407. PMID: 213009125. Freeman, GJ. et al. (2000) The Journal of experimental medicine 192, 1027-34. PMID: 110154436. Latchman, Y. et al. (2001) Nature immunology 2, 261-8. PMID: 112245277. Lin, DY. et al. (2008) Proceedings of the National Academy of Sciences of the United States of America 105, 3011-6. PMID: 182870118. Lázár-Molnár, E. et al. (2008) Proceedings of the National Academy of Sciences of the United States of America 105, 10483-8. PMID: 186411239. Yokosuka, T. et al. (2012) The Journal of experimental medicine 209, 1201-17. PMID: 22641383 | 
