PDCD1LG2

PDCD1LG2, also known as PD-L2, B7-DC, or CD273, is a gene in humans that encodes a transmembrane protein serving as a ligand for the programmed cell death protein 1 (PD-1). PD-L2 belongs to the B7 family of immune regulatory ligands and is typically expressed on professional antigen-presenting cells such as dendritic cells and macrophages; expression can be upregulated by inflammatory signals including interferon-gamma and can also be found on some B cells and thymic epithelial cells.

Functionally, engagement of PD-1 on T cells by PD-L2 delivers inhibitory signals that dampen T cell receptor–driven activation, reducing proliferation and cytokine production, and promoting peripheral tolerance. The PD-1/PD-L2 axis is a key component of the immune checkpoint network that helps restrain autoimmunity and modulate immune responses during infections and cancer. PD-L2 is thought to bind PD-1 with relatively high affinity, though the overall biological impact is context dependent.

Genetic and clinical notes: The PDCD1LG2 gene is located on chromosome 9p24.1, a region that also contains other immune-regulatory genes. In cancer, PD-L2 expression by tumor cells or tumor-associated antigen-presenting cells can contribute to immune evasion and may influence responses to therapies targeting the PD-1 pathway. While many therapies target PD-1 or PD-L1, PD-L2 contributes to the overall inhibitory signaling in the PD-1 axis.

See also: PD-1, PD-L1, B7 family, immune checkpoint.