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CD278, also known as ICOS （inducible T-cell costimulator）, is a costimulatory receptor belonging to the CD28 family, mainly expressed on activated CD4 and CD8 T cells, and weakly expressed on na?ve T cells. It is a type-1 transmembrane molecule with a single Ig V-like domain, a transmembrane region of 23 amino acids, and a cytoplasmic domain of 35 amino acids. Structurally, it is similar to CD28 and CTLA-4 but lacks the MYPPPY motif found in CD28, which is critical for binding to B7-1 and B7-2. ICOS plays a crucial role in T cell activation and differentiation, particularly in the development and maintenance of T follicular helper （Tfh） cells. It is also involved in the regulation of cytokine production and cell motility, promoting the migration of T cells to the follicle. Additionally, ICOS signaling can induce the expression of CXCR5 and Bcl6, and suppress the expression of CCR7, PSGL-1, and CD62L through the factor KLF2.