Engineering Immunological Tolerance Using Quantum Dots to Tune the Density of Self‐Antigen Display

Treatments for autoimmunity—diseases where the immune system mistakenly attacks self-molecules—are not curative and leave patients immunocompromised. New studies aimed at more specific treatments reveal that development of inflammation or tolerance is influenced by the form in which self-antigens are presented. Using a mouse model of multiple sclerosis (MS), it is shown for the first time that quantum dots (QDs) can be used to generate immunological tolerance by controlling the density of self-antigen on QDs. These assemblies display dense arrangements of myelin self-peptide associated with disease in MS, are uniform in size (<20 nm), and allow direct visualization in immune tissues. Peptide-QDs rapidly concentrate in draining lymph nodes, colocalizing with macrophages expressing scavenger receptors involved in tolerance. Treatment with peptide-QDs reduces disease incidence tenfold. Strikingly, the degree of tolerance—and the underlying expansion of regulatory T cells—correlates with the density of myelin molecules presented on QDs. A key discovery is that higher numbers of tolerogenic particles displaying lower levels of self-peptide are more effective for inducing tolerance than fewer particles each displaying higher densities of peptide. QDs conjugated with self-antigens can serve as a new platform to induce tolerance, while visualizing QD therapeutics in tolerogenic tissue domains.