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CD28 ligands, primarily comprising CD80 (B7-1) and CD86 (B7-2), are critical co-stimulatory molecules expressed on the surface of professional antigen-presenting cells (APCs) such as dendritic cells and B cells (UniProt P33681, P42081). These ligands interact with the CD28 receptor on T cells to provide the "second signal" required for full T-cell activation, proliferation, and cytokine production following the recognition of an antigen-MHC complex (PubMed: 10508230). This pathway is a fundamental regulator of the adaptive immune response, ensuring that T cells are only activated in appropriate contexts. Conversely, CD80 and CD86 also bind to the inhibitory receptor CTLA-4, which competes with CD28 with higher affinity to terminate immune responses and maintain self-tolerance (StatPearls: Abatacept). Therapeutic strategies targeting these ligands, such as the CTLA-4-Ig fusion proteins abatacept and belatacept, work by binding to CD80/CD86 and preventing their interaction with CD28 (FDA: Orencia Label). This blockade is used to treat autoimmune diseases like rheumatoid arthritis and to prevent organ rejection in transplant recipients by suppressing T-cell-mediated inflammation (PubMed: 21675897).
Binding to CD80 and CD86 on antigen-presenting cells to block their interaction with CD28 on T cells, thereby inhibiting the co-stimulatory signal required for T-cell activation.
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