Direct stimulation of naïve T cells by antigen-presenting cell vesicles

T cells are activated through T cell receptor (TCR) recognition of peptidic fragments of antigen bound to major histocompatibility complex (MHC) molecules on antigen-presenting cells (APC). In addition, T cells require a costimulatory signal delivered through contact with other ligands on APC, especially B7 and ICAM-1 which bind to CD28 and LFA-1, respectively, on T cells. Under physiological conditions, T cell activation requires contact with viable APC. Under defined conditions, however, T cells can be activated by exosomes secreted by APC. Evidence will be presented that exosomes can be directly immunogenic for CD8+ T cells in the absence of normal APC with the proviso that exosomes express a high density of MHC I/peptide complexes as well as B7 and ICAM-1. Similar findings apply to plasma membrane fragments prepared from APC sonicates.