Programmed cell death 1 ligand 2 (PD-L2) (PD-L2)

Programmed cell death 1 ligand 2 (PD-L2) is a type I transmembrane protein and a member of the B7 family of immune checkpoint molecules [1, 2]. It serves as one of the two primary ligands for the Programmed Cell Death 1 (PD-1) receptor, which is expressed on activated T-cells, B-cells, and myeloid cells [3, 5]. PD-L2 is predominantly expressed on professional antigen-presenting cells, such as dendritic cells and macrophages, and its expression is highly inducible by cytokines like IL-4 and IFN-gamma [1, 3]. In the specific context of donor dendritic cells, PD-L2 plays a pivotal role in regulating T-cell responses during transplantation and graft-versus-host disease (GVHD) by providing inhibitory signals that promote immune tolerance and suppress excessive T-cell activation [4, 5]. Binding of PD-L2 to PD-1 leads to the inhibition of T-cell receptor signaling, resulting in reduced T-cell proliferation and cytokine production [3, 5]. While PD-L1 is the more prominent target in current cancer immunotherapy, PD-L2 also contributes significantly to the immune-evasive environment of certain tumors and is a target for checkpoint inhibitor therapies that block the PD-1 pathway [1, 5].

Other names

B7-DCCD273PDCD1L2Butyrophilin B7-DCProgrammed death ligand 2

PD-1/PD-L2 pathway inhibition; blocking the interaction between PD-L2 and the PD-1 receptor to restore T-cell mediated immune responses.