4.1.2　Structure and Expression of PD-Ls

PD-1 has two identified ligands, the programmed death-1 ligand-1 (PD-L1), also known as B7-H1 or CD274 and the programmed death-1 ligand-2 (PD-L2), also known as B7-DC, or CD273.Both of them are type I transmembrane glycoproteins composed of IgC- and IgV-type extracellular domains.PD-L1and PD-L2 share about 20% amino acid identities with B7-1 and B7-2 that are ligands for CD28 and CTLA-4.The amino acid identity between PD-L1 and PD-L2 is about 40%.The interaction of PD-L2/PD-1 exhibits a 2-6-fold higher affinity and has different association/dissociation kinetics compared with the interaction of PD-L1/PD-1.If expressed at the same level, PD-L2 would be expected to outcompete PD-L1 for binding PD-1.But, PD-L2 generally expresses at a lower level may favor PD-L1 as the primary binding ligand of PD-1,except for during Th2 responses when PD-L2 is upregulated.The physiological relevance of this competition is not yet fully clear and needs further research [2].(https://www.daowen.com)

PD-L1 has a much more promiscuous expression profile.PD-L1 can express on cells of hematopoietic lineage, including activated T cells, B cells, monocytes, dendritic cells (DCs), and macrophages.It also extensively expresses on peripheral nonhemopoietic tissues, with intermediate to high expression detected in heart, skeletal muscle, placenta, lung, kidney, and liver.PD-L2 expression was initially thought to be restricted to antigen-presenting cells (APCs) such as macrophages and DCs.In recent years, however, several groups have shown that PD-L2 expression can be induced on a wide variety of other immune cells and non-immune cells depending on microenvironmental stimuli [3].