Autoimmunity to hypocretin and molecular mimicry to flu in type 1 narcolepsy

著者: Guo Luo, Aditya Ambati, Ling Lin, Mélodie Bonvalet, Markku Partinen, Xuhuai Ji, Holden T. Maecker, Emmanuel Mignot - Proceedings of the National Academy of Sciences, PNAS 2018 被引用: 193

Significance This work shows that the amidated terminal ends of the secreted hypocretin (HCRT) peptides (HCRT NH2 ) are autoantigens in type 1 narcolepsy, an autoimmune disorder targeting HCRT neurons. The autoimmune process is usually initiated by influenza A flu infections, and a particular piece of the hemagglutinin (HA) flu protein of the pandemic 2009 H1N1 strain was identified as a likely trigger. This HA epitope has homology with HCRT NH2 and T cells cross-reactive to both epitopes are involved in the autoimmune process by molecular mimicry. Genes associated with narcolepsy mark the particular HLA heterodimer (DQ0602) involved in presentation of these antigens and modulate expression of the specific T cell receptor segments (TRAJ24 and TRBV4-2) involved in T cell receptor recognition of these antigens, suggesting causality.