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CD8+ T cells from patients with narcolepsy and healthy controls recognize hypocretin neuron-specific antigens

Author

Listed:
  • Natasja Wulff Pedersen

    (Technical University of Denmark)

  • Anja Holm

    (Molecular Sleep Laboratory)

  • Nikolaj Pagh Kristensen

    (Technical University of Denmark)

  • Anne-Mette Bjerregaard

    (Technical University of Denmark)

  • Amalie Kai Bentzen

    (Technical University of Denmark)

  • Andrea Marion Marquard

    (Technical University of Denmark)

  • Tripti Tamhane

    (Technical University of Denmark)

  • Kristoffer Sølvsten Burgdorf

    (Copenhagen University Hospital, Rigshospitalet)

  • Henrik Ullum

    (Copenhagen University Hospital, Rigshospitalet)

  • Poul Jennum

    (Danish Center for Sleep Medicine)

  • Stine Knudsen

    (Danish Center for Sleep Medicine
    Oslo University Hospital)

  • Sine Reker Hadrup

    (Technical University of Denmark)

  • Birgitte Rahbek Kornum

    (Molecular Sleep Laboratory
    Danish Center for Sleep Medicine
    University of Copenhagen)

Abstract

Narcolepsy Type 1 (NT1) is a neurological sleep disorder, characterized by the loss of hypocretin/orexin signaling in the brain. Genetic, epidemiological and experimental data support the hypothesis that NT1 is a T-cell-mediated autoimmune disease targeting the hypocretin producing neurons. While autoreactive CD4+ T cells have been detected in patients, CD8+ T cells have only been examined to a minor extent. Here we detect CD8+ T cells specific toward narcolepsy-relevant peptides presented primarily by NT1-associated HLA types in the blood of 20 patients with NT1 as well as in 52 healthy controls, using peptide-MHC-I multimers labeled with DNA barcodes. In healthy controls carrying the disease-predisposing HLA-DQB1*06:02 allele, the frequency of autoreactive CD8+ T cells was lower as compared with both NT1 patients and HLA-DQB1*06:02-negative healthy individuals. These findings suggest that a certain level of CD8+ T-cell reactivity combined with HLA-DQB1*06:02 expression is important for NT1 development.

Suggested Citation

  • Natasja Wulff Pedersen & Anja Holm & Nikolaj Pagh Kristensen & Anne-Mette Bjerregaard & Amalie Kai Bentzen & Andrea Marion Marquard & Tripti Tamhane & Kristoffer Sølvsten Burgdorf & Henrik Ullum & Pou, 2019. "CD8+ T cells from patients with narcolepsy and healthy controls recognize hypocretin neuron-specific antigens," Nature Communications, Nature, vol. 10(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-08774-1
    DOI: 10.1038/s41467-019-08774-1
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    Cited by:

    1. Hanna M. Ollila & Eilon Sharon & Ling Lin & Nasa Sinnott-Armstrong & Aditya Ambati & Selina M. Yogeshwar & Ryan P. Hillary & Otto Jolanki & Juliette Faraco & Mali Einen & Guo Luo & Jing Zhang & Fang H, 2023. "Narcolepsy risk loci outline role of T cell autoimmunity and infectious triggers in narcolepsy," Nature Communications, Nature, vol. 14(1), pages 1-13, December.

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