T-cell receptor on CD8+ alpha-beta T cells specific for Inhibigen peptide-MHC class I (TCR (Inhibigen-specific))

The T-cell receptor (TCR) on CD8+ alpha-beta T cells specific for the Inhibigen peptide-MHC class I complex is a specialized immune receptor that mediates the recognition and elimination of FOXP3-expressing regulatory T cells (Tregs) (IMV Inc., 2021). The Inhibigen peptide, also known as p17, is a proprietary sequence derived from the FOXP3 transcription factor, which is the master regulator of Treg development and function (Kim et al., 2010). Although FOXP3 is primarily an intracellular protein, its degradation products are presented on the cell surface by MHC class I molecules, making them accessible to cytotoxic CD8+ T cells. When the TCR on these specific T cells binds to the Inhibigen-MHC complex, it triggers a cytotoxic response that leads to the lysis of the target Treg. This mechanism is utilized in cancer immunotherapy to deplete the immunosuppressive Treg population within the tumor microenvironment, thereby restoring the efficacy of the anti-tumor immune response (NCT03566225). Therapeutic strategies like the DPX-Inhibigen vaccine aim to expand this specific T-cell population to shift the immune balance from suppression to active tumor clearance.

Other names

FOXP3-specific T-cell receptorp17-specific T-cell receptorInhibigen-specific TCRCD8+ TCR for FOXP3 p17 epitopeT-cell receptor alpha-beta (FOXP3-specific)

Activation and expansion of antigen-specific CD8+ T cells that utilize this TCR to recognize and lyse FOXP3-expressing regulatory T cells (Tregs) via TCR-MHC class I interaction.