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CD28, a cell surface glycoprotein receptor, predominantly expressed on activated T cells, belongs to the Ig superfamily and provides a critical co-stimulatory signal. Its ligands, CD80 and CD86, are typically found on the surface of antigen-presenting cells and can either bind CD28 or CTLA-4. CD28 interacts with the CD80 dimer with relatively high affinity and the CD86 monomer with lower affinity, mediating T cell co-stimulation in conjunction with T cell receptor (TCR) signals. CD28 drives critical intracellular biochemical events including unique phosphorylation and transcriptional signaling, metabolism, and the production of key cytokines, chemokines, and survival signals that are essential for long-term expansion and differentiation of T cells. Most importantly, treatment of mice with a soluble CD28 antagonist induced antigen-specific tolerance that prevented the progression of autoimmune diseases and organ graft rejection.
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