Fig. 1

Examples of pMHC- and immunoregulatory molecule transfer via EVs or trogocytosis. a The transfer of peptide:MHC-loaded complexes by trogocytosis requires intimate cell-cell contact between APCs and T cells. During the transfer, only peptide:MHC complexes are transferred; additionally, costimulatory molecules, such as CD80/CD86, can be transferred from the APC to the T cell. Consequently, T cells can act as APCs, inducing the priming of naïve T cells. In the absence of costimulatory signals, tolerance results in T cell apoptosis and hyporesponsiveness. b Piecemeal necrosis describes the formation of an immunological synapse between peptide-loaded MHC-II⁺ HCs and CD4⁺ T cells with a cognate TCR that leads to peptide:MHC-II transfer onto CD4+ T cells. This process “eats away” part of the hepatocyte membrane and leaves behind dying HCs and CD4⁺ T cells with acquired peptide-MHC-II complexes. c HSCs transfer pMHC-I molecules to LSECs, which acquire cross-presentation abilities to elicit CD8⁺ T cell responses towards viral antigens. d Virtually all parenchymal and nonparenchymal cells produce extracellular vesicles/exosomes. Schematic representation of how pMHC-II complexes can be taken up and processed by APCs to generate alternate immune responses. First, the pMHC-II complex is taken up and presented by the APC, eliciting direct antigen presentation and CD4⁺ T cell priming in an immunological synapse that includes costimulatory molecules. Second, the MHC-II-bound peptide is taken up by the DC, processed and is consequently presented on host MHC-II molecules (blue) to elicit indirect antigen presentation and CD4⁺ T cell priming. Third, the pMHC-II complex is released by immunomodulatory EVs that carry the pMHC-II complex that confers APC properties to remote cells