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Adaptive immune receptors recognizing enhanced green fluorescent protein (eGFP) epitopes are a specialized class of T-cell receptors (TCRs) and B-cell receptors (BCRs) that identify eGFP as a foreign antigen. Although eGFP is a ubiquitous tool in molecular biology for labeling and tracking cells, its origin from the jellyfish Aequorea victoria makes it highly immunogenic in mammalian hosts, including humans and mice. These receptors mediate a robust immune response, primarily through CD8+ cytotoxic T lymphocytes that recognize eGFP-derived peptides, such as the dominant H-2Kd-restricted epitope HYLSTQSAL, presented on Major Histocompatibility Complex (MHC) molecules. This recognition leads to the targeted elimination of eGFP-expressing cells, posing a significant challenge for the long-term success of gene therapies and cell-based treatments that utilize eGFP as a reporter. In clinical and experimental settings, the activity of these receptors can be modulated by immunosuppressive drugs like tacrolimus or corticosteroids to prevent the rejection of modified cells. Furthermore, engineered versions of these receptors are utilized in universal chimeric antigen receptor (CAR) T-cell platforms, where an anti-GFP CAR-T cell targets various antigens via GFP-conjugated adapters.
Recognition of eGFP-derived peptides presented on MHC molecules, leading to T-cell activation, cytokine release, and destruction of eGFP-expressing cells.
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