PRODUCTS

Programmed cell death 1 ligand 2 (PD-L2; CD273; B7-DC) is type I transmembrane glycoprotein composed of IgC- and IgV-type extracellular domains and it is a member of the B7 gene family (1). PD-L2 can bind to programmed cell death protein 1 (PD-1) resulting in down-regulation of T cell responses (2). Compare to PD-L1, another ligand of PD-1, expression of PD-L2 is much more restricted (3). It is inducibly expressed on the surface of macrophages, dendritic cells, bone marrow derived mast cells and certain B cell populations (3) (4) (5). The PD-L2 expression is mainly induced by Interleukin 4 (IL-4) and granulocyte-macrophage colony-stimulating factor (GM CSF) and to lesser extent by Interferon-γ (IFN-γ) (5). As PD-L1 and PD-L2 can inhibit effector T cell proliferation and cytokine production, the PD-L:PD-1 pathway is an appealing therapeutic target (2). Blocking the PD-1 pathway enhance anti-tumor immunity, while stimulating this pathway may be useful for down-regulating ongoing immune responses in transplant rejection and autoimmune and allergic diseases (2).

1. Okazaki T and Honjo T. PD-1 and PD-1 ligands: from discovery to clinical application. International Immunology. 2007, Vol. 19, 7, pp. 813–824.
2. Latchman Y et al. PD-L2 is a second ligand for PD-1 and inhibits T cell activation. Nature Immunology. 2001, Vol. 3, 2, pp. 261-268.
3. Keir ME et al. PD-1 and Its Ligands in Tolerance and Immunity. The Annual Review of Immunology. 2008, 26, pp. 677–704.
4. Zak KM et al. Structural Biology of the Immune CheckpointReceptor PD-1 and Its Ligands PD-L1/PD-L2. Structure. 2017, 25, pp. 1163-1174.
5. Riella LV et al. Role of the PD-1 Pathway in the Immune Response. American Journal of Transplantation. 2012, 12, pp. 2575–2587.