Dr. Emmanuel Mignot discovered that narcolepsy is caused by the loss of the ~20,000 hypothalamic neurons that secrete the wake-promoting peptide hypocretin. He identified HLA-DQB1*06:02 and T-Cell receptor genes as major susceptibility genes, which act together to promote a highly selective T cell-mediated autoimmune process triggered by influenza infection. Applying lessons learned from narcolepsy immunogenetics, Dr. Mignot has found a protective signal in an immune gene called HLA-DR, specifically the presence of the HLA-DRB1*04 (DR4) subtype in Parkinson’s disease (PD). Dr. Mignot plans to study DR4 association in larger cohort of 30,000 PD cases, examine its associations with PD brain pathology such as Lewy body density and characterize alpha-Synuclein peptides that bind DR4s and activate immune cells in PD cases. Understanding the mechanism of how DR4s mediates protection against PD could be used to slow down or stop PD progression