Proposed model for antigen presentation by astrocytes in the PD brain. Astrocytes ingest large amounts of αSYN-F, which can either enter the endo-lysosomal pathway or be released into the cytosol and processed via the proteasome pathway. Proteosomal digestion of the αSYN-F results in 8–10 aa long fragments that are transported to the ER to encounter MHC-I molecules. The MHC-I/αSYN complexes are then transported to the cell surface to be presented to CD8+ T cells. The αSYN-F that follow endo-lysosomal pathway are fragmented to pieces of 12–24 long aa that meet MHC-II in the late endosomes. Subsequently, The MHC-II/αSYN complexes are transported to the cell surface to be presented to CD4+ T cells. Activation of the CD4+ T cells requires surface expression of CD80 and CD86. Our results demonstrate that these receptors are only present on the human astrocytes that had engulfed αSYN-F.