Figure 2.

Potential scenarios of EV involvement in the fetal allorecognition by maternal T cells. Maternal cells are shown in blue and fetal cells and EVs are shown in red. Up: Direct pathway. Fetal APCs, which secrete EVs to the intercellular space, present peptides (auto- or alloantigens) via MHC (I or II) molecules to immunocompetent maternal T cells. Middle: In the semi-direct pathway, fetal allogeneic MHC molecules (I or II) are acquired via capture and uptake of fetal cells (entire or only their cell membrane) or their secreted EVs, and then recycled and expressed on the maternal APC surface. APC can present antigens bound to fetal MHC molecules to maternal T cell receptors. The indirect pathway implies the processing of fetal proteins from EVs or cells and the presentation of deriving peptides by maternal MHC II complexes to T maternal cells. Down: Fetal-derived EVs cross-decorate maternal APCs with intact MHC-peptide complexes that can be recognized by T cells similar to the semi-direct pathway. All displayed processes involve co-stimulatory interactions between APCs and T cells which are decisive for subsequent reactions, which may be tolerogenic, immunoregulatory or –stimulatory. The figure was drawn using pictures from 105 (http://smart.servier.com/) and was based on previous revisions (5, 116).