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PD-1 is involved in immune tolerance by suppressing activated immune cells via interaction with its ligands. Two known ligands of PD-1 are PD-L1 and PD-L2. PD-L1 is a 290 aa transmembrane glycoprotein. PD-L2 (B7DC) may lead to local cytokine production that is beneficial to the tumor cells. PD-L1 and PD-L2 play different roles in the immune regulatory process. PD-L1 inhibits T-cell function in peripheral tissues, whereas PD-L2 suppresses immune T-cell activation in lymphoid organs.
NKG2A Immune Checkpoint Natural killer group protein 2A (NKG2A) is a cell surface receptor and member of the NKG2 family that can form a heterodimer with CD94 on the cell surface, also known as KLRD1, another NK cell-expressed C-type lectin. The non-classical MHC class I molecule HLA-E is the major ligand of NKG2A-CD94. These inhibitory receptors interact with MHC I ligands on target cells, leading to complete inhibition of NK cell granule polarization and cytotoxic granule release prevention.
LAG-3 immune checkpoint plays an important role in T cell proliferation and activation as a negative regulator of these processes. Along with other inhibitory receptors, LAG-3 helps to keep cytotoxic CD8+ T cells in an exhausted state during highly inflammatory environments such as a chronic viral infection. LAG-3 has also been implicated in memory T cell expansion, Treg function, and the activation and maturation of dendritic cells.