The loss of hypothalamic hypocretin/orexin (hcrt) producing neurons causes 
narcolepsy with cataplexy. An autoimmune basis for the disease has long been 
suspected and recent results have greatly strengthened this hypothesis. 
Narcolepsy with hcrt deficiency is now known to be associated with a Human 
Leukocyte Antigen (HLA) and T-cell receptor (TCR) polymorphisms, suggesting that 
an autoimmune process targets a single peptide unique to hcrt-cells via specific 
HLA-peptide-TCR interactions. Recent data have shown a robust seasonality of 
disease onset in children and associations with Streptococcus Pyogenes, and 
influenza A H1N1-infection and H1N1-vaccination, pointing towards processes such 
as molecular mimicry or bystander activation as crucial for disease development. 
We speculate that upper airway infections may be common precipitants of a whole 
host of CNS autoimmune complications including narcolepsy.