CD4+ T cell autoimmunity to hypocretin/orexin and cross-reactivity to A 2009 h1n1 influenza a epitope in narcolepsy

Alberto K. De La Herrán-Arita, Birgitte Rahbek Kornum, Josh Mahlios, Wei Jiang, G. Lin, Tieying Hou, Claudia Macaubas, Mali Einen, Giuseppe Plazzi, Catherine Crowe, Evan W. Newell, Mark M. Davis, Elizabeth D. Mellins, Emmanuel Mignot

Research output: Contribution to journalArticle

Abstract

Narcolepsy, a disorder strongly associated with human leukocyte antigen (HLA)-DQA1*01:02/DQB1*06:02 (DQ0602), is characterized by excessive daytime sleepiness, cataplexy, and rapid eyemovement sleep abnormalities. It is caused by the loss of ∼70,000 posterior hypothalamic neurons that produce the wake-promoting neuropeptide hypocretin (HCRT) (orexin). We identified two DQ0602-binding HCRT epitopes, HCRT56-68 and HCRT87-99, that activated a subpopulation of CD4+ T cells in narcolepsy patients but not in DQ0602-positive healthy control subjects. Because of the established association of narcolepsy with the 2009 H1N1 influenza A strain (pH1N1), we administered a seasonal influenza vaccine (containing pH1N1) to patients with narcolepsy and found an increased frequency of circulating HCRT56-68- and HCRT87-99-reactive T cells. We also identified a hemagglutinin (HA) pHA1 epitope specific to the 2009 H1N1 strain, pHA1275-287, with homology to HCRT56-68 and HCRT87-99. In vitro stimulation of narcolepsy CD4+ T cells with pH1N1 proteins or pHA1 275-287 increased the frequency of HCRT56-68- and HCRT87-99-reactive T cells. Our data indicate the presence of CD4+ T cells that are reactive to HCRT in narcolepsy patients and possible molecular mimicry between HCRT and a similar epitope in influenza pH1N1, pHA1275-287.

Original languageEnglish
Article number216ra176
JournalScience Translational Medicine
Volume5
Issue number216
DOIs
Publication statusPublished - Dec 18 2013

ASJC Scopus subject areas

  • Medicine(all)

Fingerprint Dive into the research topics of 'CD4<sup>+</sup> T cell autoimmunity to hypocretin/orexin and cross-reactivity to A 2009 h1n1 influenza a epitope in narcolepsy'. Together they form a unique fingerprint.

  • Cite this

    De La Herrán-Arita, A. K., Kornum, B. R., Mahlios, J., Jiang, W., Lin, G., Hou, T., Macaubas, C., Einen, M., Plazzi, G., Crowe, C., Newell, E. W., Davis, M. M., Mellins, E. D., & Mignot, E. (2013). CD4+ T cell autoimmunity to hypocretin/orexin and cross-reactivity to A 2009 h1n1 influenza a epitope in narcolepsy. Science Translational Medicine, 5(216), [216ra176]. https://doi.org/10.1126/scitranslmed.3007762