Tolerance induction with quantum dots displaying tunable densities of self-antigen

Abstract

During autoimmune diseases like type 1 diabetes or multiple sclerosis (MS), the immune system mistakenly recognizes and attacks healthy tissues in the body. In MS, myelin, which surrounds and protects the axons of neurons, is attacked by inflammatory cells leading to neurodegeneration. The current standard of care for MS patients is regular injection of immunosuppressive drugs that non-specifically suppress immune function, leaving patients immunocompromised and open to opportunistic infection. New investigations aim to address this problem with immunotherapy-based strategies that promote myelin-specific tolerance. Recent reports reveal that the development of inflammation or tolerance against certain molecules is influenced by the concentration and form of self-antigen presented to immune cells (i.e. free, particle).Strategies that allow tunable delivery of self-antigen are therefore of great interest to further probe these connections. Quantum dots (QDs) were chosen as the nanomaterial to investigate these questions because they can be conjugated with a large and controllable number of biomolecules.Additionally, their size facilitates rapid drainage through lymphatics to lymph nodes (LNs), where they accumulate and can be visualized by deep-tissue imaging due to their intrinsic fluorescence. QDs could be decorated with up to 130 myelin oligodendrocyte glycoprotein (MOG) peptides, a known self-antigen of MS (Fig 1A). Please click Additional Files below to see the full abstract