Figure 1.

Possible mechanism of action of APC-targeted LNP-mRNA. Targeted mRNA-LNP-cell interaction is mediated by specific ligands that bind to APC cell surface receptor. Receptor activation might lead to IFNs and other cytokine/chemokine production (1). Following endocytosis (2), mRNA in the endosome can interact with membrane-bound Toll-like receptors (3). Triggering of TLR activates signal transduction pathways that selectively lead to production of Type I IFNs and/or pro-inflammatory cytokines. (4) Entrapped mRNA then undergoes endosomal escape and is released into the cytosol where it is translated by ribosomes (5). Upon translation, the protein can be secreted out of the host cell or processed into smaller peptides by proteasome. Proteins secreted extracellularly (7a) can be taken up by other antigen presenting cells (APCs) (8a) and then degraded into peptides subsequently presented on the cell surface by MHC class II molecules (9) for recognition by CD4⁺ T lymphocytes (10). Alternatively, translated proteins are degraded by the proteasome into peptides in the same cell (6). The generated antigenic peptides are then transported into the endoplasmic reticulum and loaded onto major histocompatibility complex (MHC) class I and/or Class II molecules, as less common pathway (7b). The loaded MHC - peptide epitope complexes are then presented on the surface of the APC and may bind the T cell receptor (TCR) of CD8⁺ and/or CD4⁺ T lymphocytes (8b).