Sleep Disorders / 2014 / Article / Fig 1

Review Article

Narcolepsy as an Immune-Mediated Disease

Figure 1

(a) Molecular mimicry describes the activation of cross-reactive TH1 cells that recognize both the microbial epitope [I] and the autoantigen [II]. Activation of the cross-reactive T cells results in the release of cytokines and chemokines [III] that recruit and activate monocytes and macrophages, which mediate self-tissue damage. The subsequent release of self-tissue antigens and their uptake by APCs perpetuates the autoimmune disease [IV]. (b) Molecular mimicry at the MHC/TCR synapses level. Molecular mimicry between infectious agents (H1N1 and/or streptococcus pyogenes) and hypocretin neuron autoantigens. Sequence and structural homology between foreign [I] and self-peptides [II] are required for molecular mimicry to occur. The MHC binding groove selects the peptide fragment with a specific amino acid sequence in the context of DQA1*01:02-DQB1*06:02. The TCR recognizes a presented peptide with a specific amino acid sequence [I and II]. Activated CD4+ T cells cross-react and recognize hypocretin neuron autoantigens as foreign molecules, prompting an autoimmune response against hypocretin neurons [II].

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