20 April 2022

Saponin-based adjuvants (SBAs) are promising new adjuvants that stand out as they not only enforce CD4 + T cell-mediated immunity and antibody responses, but also induce an unprecedented level of antigen cross-presentation by dendritic cells (DC) and subsequent CD8 + T cell activation. This was published in Cellular and Molecular Life Sciences.

Lisa Huis in ‘t Veld, Nataschja Ho and colleagues from the team of Gosse Adema at the Radiotherapy & OncoImmunology (ROI) lab, theme Cancer development and immune defense discovered that SBA's ability to boost cross-presentation depends on the induction of lipid bodies. Moreover, the MHCII-low CD11b-high DC subset was identified to be most responsive to SBA-induced cross-presentation.

The aim is to further unravel the mechanisms behind the induction of DC cross-presentation by SBAs. Here we show that SBAs specifically induce the PKR-like Endoplasmic Reticulum kinase (PERK) pathway and that SBA-induced DC cross-presentation is dependent on activation of the PERK pathway. PERK activation and lipid body formation are both crucial for SBA-induced cross-presentation and PERK inhibition has little or no effect on SBA-induced lipid body formation. SBA's responsiveness, lipid body formation and PERK activation are specific for the MHCII-low CD11b-high DCs.

These findings contribute to understanding the pathways involved in SBA-induced cross-presentation and immune activation which will ultimately lead to the development of vaccines with improved efficiency and safety.

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