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

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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. / CD8+ T cells from patients with narcolepsy and healthy controls recognize hypocretin neuron-specific antigens. I: Nature Communications. 2019 ; Bind 10, Nr. 1. s. 837.

Bibtex

@article{51ad35b497c448938d18a613dab18f3f,
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.",
keywords = "Adolescent, Adult, CD8-Positive T-Lymphocytes/immunology, Case-Control Studies, Child, Female, Genetic Predisposition to Disease, HLA-DQ beta-Chains/genetics, Humans, Male, Middle Aged, Narcolepsy/genetics, Neurons/metabolism, Orexins/immunology, Peptides/immunology",
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",
month = "12",
day = "1",
doi = "10.1038/s41467-019-08774-1",
language = "English",
volume = "10",
pages = "837",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",

}

RIS

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 - 2019/12/1

Y1 - 2019/12/1

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.

KW - Adolescent

KW - Adult

KW - CD8-Positive T-Lymphocytes/immunology

KW - Case-Control Studies

KW - Child

KW - Female

KW - Genetic Predisposition to Disease

KW - HLA-DQ beta-Chains/genetics

KW - Humans

KW - Male

KW - Middle Aged

KW - Narcolepsy/genetics

KW - Neurons/metabolism

KW - Orexins/immunology

KW - Peptides/immunology

U2 - 10.1038/s41467-019-08774-1

DO - 10.1038/s41467-019-08774-1

M3 - Journal article

VL - 10

SP - 837

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

IS - 1

M1 - 837

ER -

ID: 58007203