(648a) Directing Immune Tolerance Using Quantum Dots to Control Self-Antigen Display and Stop Autoimmunity

During multiple sclerosis (MS) the immune system mistakenly attacks the myelin insulating neurons, resulting in debilitating loss of motor function. Current MS treatments are not curative and leave patients immunocompromised, highlighting the need for therapies that provide selective tolerance against myelin without broad suppression. Lymph nodes (LNs) play an important role in controlling responses to self-antigens. Intriguingly, new studies reveal inflammation or tolerance is influenced by the form antigen is presented in LNs by triggering natural regulatory pathways involved in clearance of apoptotic cell debris. Thus, efficient delivery of self-antigen to LNs with control over peptide morphology or display density could support more specific therapies. We used simulation to design nanocrystalline quantum dots (QDs) that display dense arrangements of myelin self-peptides. These peptide-QD conjugates are uniform in size (<20 nm) and enable tunable display of 10-150 peptides per QD. In mice, the conjugates concentrate in LNs, localizing to domains involved in maintaining tolerance against apoptotic self cells. The intrinsic fluorescence of the QDs allows direct visualization of this trafficking. During a pre-clinical mouse model of MS, treatment with peptide-QDs reduces incidence 10-fold and decreases disease severity. Strikingly, the degree of tolerance depends on the density of peptides installed on the QDs. This is the first time QDs have been used to promote tolerance, creating an opportunity to combat autoimmunity by both controlling peptide display density and visualizing the processing of these ligands.