Programmed cell death 1 ligand 2 (also known as PD-L2, B7-DC) is a protein that in humans is encoded by the PDCD1LG2 gene. PDCD1LG2 has also been designated as CD273 (cluster of differentiation 273). PDCD1LG2 is an immune checkpoint receptor ligand which plays a role in negative regulation of the adaptive immune response. PD-L2 is one of two known ligands for Programmed cell death protein 1 (PD-1). PD-L2 binds to its receptor PD-1 with dissociation constant Kd of 11.3 nM. Binding to PD-1 can activate pathways inhibiting TCR/BCR-mediated immune cell activation (for a more detailed discussion see PD-1 signaling). PD-L2 plays an important role in immune tolerance and autoimmunity. Both PD-L1 and PD-L2 can inhibit T cell proliferation and inflammatory cytokine production. Blocking PD-L2 has been shown to exacerbate experimental autoimmune encephalomyelitis. Unlike PD-L1, PD-L2 has been shown activate the immune system. PD-L2 triggers IL-12 production in murine dendritic cells leading to T cell activation. Others have shown that treatment with PD-L2 Ig led to T helper cell proliferation.