Synthetic Long Peptide technology
1. The long peptide is taken up by the dendritic cell
2. The long peptide enters the proteosome, where it is degraded into small pieces, containing epitopes recognized by T cells. The epitopes are a mix of T helper (Th) epitopes and cytotoxic T cell (CTL) epitopes. The Th epitopes (red) enter the MHC Class II presentation pathway (3a). At the same time, the CTL epitopes (yellow) enter the MHC class I presentation pathway (3b).
MHC class II presentation
3a. Th epitopes are transported to small compartments, containing MHC class II molecules, called endosomes.
4a. In the endosome the Th epitope binds to the MHC class II molecule.
5a. The MHC-epitope complex is expressed on the cell surface. The epitope presented by the MHC class II is recognized by the T cell receptor (pink) of a CD4 Th cell.
6a. The CD4 Th cell receptor binds to the MHC-epitope complex followed by binding of CD40 ligand (green) expressed on the Th cell to CD40 (blue) expressed by the DC. These interactions result in activation of the Dendritic Cell.
7a. The activated Dendritic Cell (DC) is thus licensed by the CD4 T cell to provide the appropriate signals to the CD8 CTL for full CD8 cytotoxic T cell activation. Furthermore, it signals to the CD8 CTL by release of soluble products to further stimulate CD8 T cell activation and expansion.
MHC class I presentation
3b. The CTL epitopes enter the ER.
4b. In the ER, the CTL epitopes bind to newly formed MHC class I.
5b. The MHC-epitope complex is transported from the ER to the cell surface.
6b. The MHC-peptide complex is displayed on the cell surface.
7b. The MHC-peptide complex is recognized by the T cell receptor (green) on a CD8 cytotoxic T cell. At the same time, co-stimulatory molecules expressed on the DC (purple) interact with receptors for such co-stimulatory molecule (red).
Outside the cell
8. These three signals (T cell receptor binding to MHC-epitope complex, co-stimulation and T helper signals) ensure optimal activation of the CD8 T cell. This activation leads to expansion of the CTL.
9. Active CD8 T cells will move to tumor cells that express the same epitopes.
10. The active CD8 T cells kill the tumor cells.