1. CD8 + T cells from patients with narcolepsy and healthy controls recognize hypocretin neuron-specific antigens.
- Author
-
Pedersen NW, Holm A, Kristensen NP, Bjerregaard AM, Bentzen AK, Marquard AM, Tamhane T, Burgdorf KS, Ullum H, Jennum P, Knudsen S, Hadrup SR, and Kornum BR
- Subjects
- Adolescent, Adult, Case-Control Studies, Child, Female, Genetic Predisposition to Disease, Humans, Male, Middle Aged, Narcolepsy genetics, Neurons metabolism, Orexins metabolism, CD8-Positive T-Lymphocytes immunology, HLA-DQ beta-Chains genetics, Narcolepsy immunology, Orexins immunology, Peptides immunology
- 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.- Published
- 2019
- Full Text
- View/download PDF