Lymphocyte costimulatory molecule

Lymphocyte costimulatory molecules are a diverse group of transmembrane glycoproteins expressed primarily on T lymphocytes that provide essential secondary signals required for full activation following antigen recognition by the T cell receptor. These molecules belong mainly to two structural families—the immunoglobulin superfamily including key receptors like CD28 and ICOS—and the tumor necrosis factor receptor superfamily including OX40 and 4‑1BB. Their engagement with ligands expressed predominantly on antigen-presenting cells amplifies primary signaling cascades leading to enhanced transcription factor activity such as NFAT and NFκB. This promotes critical biological outcomes including cytokine production like interleukin‑2 secretion, cellular proliferation, survival by inhibiting apoptosis pathways, metabolic changes within activated lymphocytes, cytoskeletal remodeling necessary for synapse formation between immune cells, and ultimately effective adaptive immunity. Therapeutically manipulating these pathways has become central in treating cancers through checkpoint inhibitors that unleash anti-tumor immunity as well as controlling autoimmune diseases by dampening excessive lymphocyte activation[1][3][6].

Other names

Costimulatory moleculesT cell costimulatory receptorsImmune costimulators

Drugs modulate these targets by: - Blocking stimulatory signals to inhibit unwanted T cell activation in autoimmunity or transplant rejection. - Enhancing stimulatory signals or blocking inhibitory receptors to boost anti-tumor immunity. For example, CTLA4-Ig fusion proteins bind CD80/CD86 on antigen-presenting cells preventing their interaction with CD28 on T cells, thus inhibiting co-stimulation[3][6].