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*, Birgitte Rahbek Kornum

*Corresponding author for this work

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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.
Original languageEnglish
Article number837
JournalNature Communications
Volume10
Issue number1
Number of pages12
ISSN2041-1723
DOIs
Publication statusPublished - 2019

Cite this

@article{5b7b0f369fa1447aa15f50abc1daae4a,
title = "CD8+ T cells from patients with narcolepsy and healthy controls recognize hypocretin neuron-specific antigens",
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.",
author = "Pedersen, {Natasja Wulff} and Anja Holm and Kristensen, {Nikolaj Pagh} and Anne-Mette Bjerregaard and Bentzen, {Amalie Kai} and Marquard, {Andrea Marion} and Tripti Tamhane and Burgdorf, {Kristoffer S{\o}lvsten} and Henrik Ullum and Poul Jennum and Stine Knudsen and Hadrup, {Sine Reker} and Kornum, {Birgitte Rahbek}",
year = "2019",
doi = "10.1038/s41467-019-08774-1",
language = "English",
volume = "10",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",

}

CD8+ T cells from patients with narcolepsy and healthy controls recognize hypocretin neuron-specific antigens. / Pedersen, Natasja Wulff; Holm, Anja; Kristensen, Nikolaj Pagh; Bjerregaard, Anne-Mette; Bentzen, Amalie Kai; Marquard, Andrea Marion; Tamhane, Tripti; Burgdorf, Kristoffer Sølvsten; Ullum, Henrik; Jennum, Poul; Knudsen, Stine; Hadrup, Sine Reker; Kornum, Birgitte Rahbek.

In: Nature Communications, Vol. 10, No. 1, 837, 2019.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - CD8+ T cells from patients with narcolepsy and healthy controls recognize hypocretin neuron-specific antigens

AU - Pedersen, Natasja Wulff

AU - Holm, Anja

AU - Kristensen, Nikolaj Pagh

AU - Bjerregaard, Anne-Mette

AU - Bentzen, Amalie Kai

AU - Marquard, Andrea Marion

AU - Tamhane, Tripti

AU - Burgdorf, Kristoffer Sølvsten

AU - Ullum, Henrik

AU - Jennum, Poul

AU - Knudsen, Stine

AU - Hadrup, Sine Reker

AU - Kornum, Birgitte Rahbek

PY - 2019

Y1 - 2019

N2 - 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.

AB - 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.

U2 - 10.1038/s41467-019-08774-1

DO - 10.1038/s41467-019-08774-1

M3 - Journal article

VL - 10

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

IS - 1

M1 - 837

ER -