Fig. 1. Structures of natural and synthetic QS-based saponin adjuvants and proposed mechanism of action for QS-21-related saponin adjuvants.
a | Structures of saponin natural product adjuvants QS-21, QS-18 and QS-17 derived from the Quillaja saponaria tree17 and summary of structure–adjuvant activity relationships of QS-21 (ref.36). b | Structures of saponin natural product adjuvant QS-7Xyl (ref.17) and summary of QS-7 structure–adjuvant activity relationships29,43. c | Schematic representation of the proposed mechanism of action for QS-21-related saponin adjuvants48. Upon endocytosis, exogenous protein antigens and QS-21 are delivered to dendritic cells (DCs). Following QS-21-mediated disruption of the endosomal membrane, cleaved protein antigens can be further processed into smaller peptide fragments in the cytosol by the proteasome machinery. Degraded peptides are translocated into the endoplasmic reticulum (ER) by transporter molecules, where chaperones facilitate their binding to newly synthesized MHC class I (MHC-I) molecules for vesicular migration through the Golgi to the cell surface. Finally, peptide epitopes exposed on the DC surface in association with MHC-I molecules are presented to naive CD8+ T cells (cross-presentation) through the T cell receptor (TCR). TH, T helper. Part c adapted from ref.47, CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/), and with permission from ref.53, Elsevier.