Fig. 2. Structures of natural and synthetic α-GalCer-based adjuvants and mechanism of action of α-GalCer.
a | Structure of natural α-galactosylceramide (α-GalCer) and key structural modifications and their impact on activity and cytokine profile production60. b,c | Structures of synthetic α-GalCer variants inducing T helper 2 (TH2)-biased (OCH, panel b)87 and TH1-biased (7DW8-5, panel c)96 responses. d | Schematic representation of invariant natural killer T (iNKT) cell activation and α-GalCer mechanism of action120. α-GalCer presentation on antigen-presenting cell (APC) surface in association with CD1d enables activation of iNKT cells by interaction with their invariant T cell receptor (iTCR). iNKT cells rapidly secrete both pro-inflammatory (TH1) and anti-inflammatory (TH2) cytokines, such as interferon-γ (IFNγ) and interleukin-4 (IL-4), respectively. Depending on several factors, including the nature of the glycolipid antigen, its loading mode into CD1d protein, cytokine milieu, cell types that present the glycolipid antigen, co-stimulatory interactions and frequency of treatment, activated iNKT cells can exhibit a diverse range of responses on other cell types, such as B and T lymphocytes, macrophages, dendritic cells and NK cells. Part d adapted with permission from ref.60, ACS, from ref.63, CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/), and with permission from ref.120, Future Medicine.