The loss of dopaminergic neurons during Parkinson’s disease (PD) is responsible for the hallmark motor impairment associated with the disease. The molecular mechanisms driving the disease process are still poorly understood. While the contribution of inflammation in PD is well established, a growing body of evidence supports a role for the long-lasting adaptive immune system in the disease. We showed that, in inflammatory conditions, the PD-proteins PINK1 and Parkin negatively regulate the presentation of mitochondrial antigens on MHC I molecules, a process referred to as MitAP (Mitochondrial Antigen Presentation). In the absence of PINK1, over-activation of this pathway engages autoimmune mechanisms leading to the activation of cytotoxic CD8+ T cells that may contribute to dopaminergic neurons (DNs) cell death. Using pharmacological and genetic approaches, together with OMICs analyses, we characterized here the MitAP pathway at the molecular cell level. Our data indicate that engagement of TLR4 during inflammation sequentially activates the stimulator of interferon genes (STING) and the unfolded protein response (UPR) to regulate both the innate inflammatory response and antigen presentation. Remarkably, the role of STING and the UPR in the presentation of self-antigens is regulated by LRRK2, a protein with GTPase and kinase activities linked with PD. These data highlight the fact that immune processes could be targeted for the development of therapeutic approaches to prevent or delay the onset of PD