Human B7-H2, also known as ICOS ligand (ICOSL) or CD275, is a member of the B7 family of costimulatory molecules that plays a central role in regulating adaptive immune responses. It is expressed primarily on antigen-presenting cells—including dendritic cells, B cells, monocytes, and macrophages—as well as on certain endothelial and epithelial cells, particularly following inflammatory stimulation. B7-H2 binds to its receptor ICOS (Inducible T cell Co-Stimulator) on activated T cells, delivering a critical costimulatory signal that promotes T cell proliferation, survival, cytokine production (including IL-4, IL-10, and IL-21), and differentiation. The B7-H2–ICOS pathway is especially important for T follicular helper (Tfh) cell development, germinal center formation, immunoglobulin class switching, and long-lived plasma cell responses, making it essential for effective humoral immunity. Dysregulation of B7-H2 signaling has been implicated in autoimmune diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis, and inflammatory bowel disease, as well as in allergic disorders, chronic infections, and tumor immune evasion. In clinical and translational research, human B7-H2 is studied as a key regulator of T cell–B cell interactions and as a potential therapeutic target in immuno-oncology, autoimmunity, and vaccine development.