Figure 2.

Possible immune mechanisms inducing narcolepsy via molecular mimicry and/or epitope spreading.

Molecular mimicry. CD4 T cell-mediated activation: after being processed by an antigen presenting cell, H1N1 influenza peptides are presented associated to MHC class II molecule (HLA-DQB1*06:02) to CD4+ T cell, that in turn, through cytokine secretion, activate B cells and/or CD8+ T cell that are cross reactive with hypocretin-producing neurons. CD8+ T cell response: after being processed by an antigen presenting cell, H1N1 influenza peptides are presented associated to MHC class I molecule to CD8+ T cell, that in turn will attack hypocretin-producing neurons by cross-reactivity. B cell response: After being activated with H1N1 Influenza, B cells will secrete H1N1-specific antibodies that are cross-reactive with hypocretin-producing neurons. Epitope spreading: after immune response against H1N1 Influenza virus caused tissue damages (macrophages), some self peptides are released and treated by APC as antigens, meaning they are presented to CD4+ T cells that in turn initiate an immune response against self antigens.