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

Natasja Wulff Pedersen, Anja Holm, Nikolaj Pagh Kristensen, Anne-Mette Bjerregaard, Amalie Kai Bentzen, Andrea Marion Marquard, Tripti Tamhane, Kristoffer Sølvsten Burgdorf, Henrik Ullum, Poul Jennum, Stine Knudsen, Sine Reker Hadrup () and Birgitte Rahbek Kornum ()
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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
Sine Reker Hadrup: Technical University of Denmark
Birgitte Rahbek Kornum: Molecular Sleep Laboratory

Nature Communications, 2019, vol. 10, issue 1, 1-12

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41467-019-08774-1

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