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Nat Commun. 2019 Feb 19;10(1):837. doi: 10.1038/s41467-019-08774-1.

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

Author information

1
Department of Health Technology, Section of Experimental and Translational Immunology, Technical University of Denmark, 2800 Kgs Lyngby, Denmark.
2
Department of Clinical Biochemistry, Molecular Sleep Laboratory, Rigshospitalet, 2600 Glostrup, Denmark.
3
Department of Clinical Immunology 2034, Copenhagen University Hospital, Rigshospitalet, 2100 Copenhagen, Denmark.
4
Department of Clinical Neurophysiology, Danish Center for Sleep Medicine, Rigshospitalet, 2600 Glostrup, Denmark.
5
Norwegian Centre of Expertise for Neurodevelopmental Disorders and Hypersomnias (Nevsom), Department of Rare Disorders, Oslo University Hospital, Ullevål, 0424 Oslo, Norway.
6
Department of Health Technology, Section of Experimental and Translational Immunology, Technical University of Denmark, 2800 Kgs Lyngby, Denmark. sirha@dtu.dk.
7
Department of Clinical Biochemistry, Molecular Sleep Laboratory, Rigshospitalet, 2600 Glostrup, Denmark. kornum@sund.ku.dk.
8
Department of Clinical Neurophysiology, Danish Center for Sleep Medicine, Rigshospitalet, 2600 Glostrup, Denmark. kornum@sund.ku.dk.
9
Department of Neuroscience, University of Copenhagen, 2200 Copenhagen, Denmark. kornum@sund.ku.dk.

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.

PMID:
30783092
PMCID:
PMC6381094
DOI:
10.1038/s41467-019-08774-1
[Indexed for MEDLINE]
Free PMC Article

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