Immune Checkpoint PD1, PD-L1, PD-L2

Immune checkpoints play role to prevent an immune response from being so strong that it destroys healthy cells in the body. Immune checkpoint inhibitors are approved to treat some people with a variety of cancer types.

CTLA-4 is a member of the CD28-B7 superfamily and acts as a co-inhibitory receptor for T-cell activation.

PD-1 and its receptors. Programmed Cell Death Protein 1 (PD-1) is a checkpoint protein on T cells and plays a vital role in inhibiting immune responses and promoting self-tolerance through modulating the activity of T-cells, activating apoptosis of antigen-specific T cells and inhibiting apoptosis of regulatory T cells. Programmed Cell Death Ligand as PD1’s receptor, including ligand 1 (PD-L1), ligand 2 (PD-L2) are commonly expressed on dendritic cells and macrophages, and its ectodomain is composed of a membrane distal IgSF V-set and a membrane proximal IgSF C-set domain. PD-L1 is considered to be a co-inhibitory factor of the immune response, it can combine with PD-1 to reduce the proliferation of PD-1 positive cells, inhibit their cytokine secretion and induce apoptosis. PD-L2 binding to PD1 has higher affinity than PD-L1, acting to suppress T-cell proliferation, cytokine production, and immune-mediated tumor destruction.

ITIM domains (TIGIT) is an immune receptor present on a fraction of T cells and natural killer (NK) cells. TIGIT binds to CD155 with higher affinity and CD112 with lower affinity.