CD28

CD28, officially designated as Cluster of Differentiation 28, is a critical co-stimulatory receptor predominantly expressed on T cells. It binds to CD80 (B7-1) or CD86 (B7-2) ligands on antigen-presenting cells, delivering a secondary activation signal that synergizes with T-cell receptor (TCR) engagement to promote T-cell proliferation, cytokine production, and survival. This interaction is pivotal for adaptive immunity, with its signaling pathway involving PI3K/AKT, MAPK, and NF-κB cascades. Dysregulation of CD28 is implicated in autoimmune disorders (e.g., rheumatoid arthritis), immunodeficiency, and cancer immune evasion. Therapeutic strategies targeting CD28 include CTLA-4-Ig fusion proteins (e.g., abatacept) that block CD28-B7 interactions to suppress autoimmune responses. Conversely, CD28 co-stimulatory domains are engineered into chimeric antigen receptor (CAR) T cells to enhance antitumor efficacy. Agonistic anti-CD28 antibodies, though historically challenging due to safety risks, are being re-evaluated in controlled contexts for immunostimulation in oncology. Recent trials explore modulating CD28 signaling to balance immune activation and tolerance.