Regulation of immune responses by professional APCs.

Professional APCs, such as DCs, present MHC class I and II complexes with peptides (p-MHC) that are derived from captured exosomes. (A) EVs retained on the APC surface present their p-MHC complexes directly to T cells, where costimulatory molecules and other regulatory molecules can be provided by the APC (cross-dressing). The EVs also can be internalized, allowing them to transfer their peptides to MHC molecules of the host APCs. Endogenous antigens can be processed in a similar manner, and the resulting epitopes are loaded onto MHC class II molecules. Host MHC class II complexed with EV-derived peptides (p-MHC II) are transported to the cell surface for presentation to T cells. (B) Alternatively, EV interaction with and uptake by APCs can lead to increased production of cytokines, such as TGF-β1, and release of APC-derived EVs carrying p-MHC II that are able to regulate antigen-specific immune responses. For simplicity, only MHC class II complexes are shown, but similar events can occur for presentation of EV-derived peptides on MHC class I for presentation to CD8⁺ T cells.