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CD8+ T cells from patients with narcolepsy and healthy controls recognize hypocretin neuron-specific antigens.
- Source :
- Nature Communications; 2/19/2019, Vol. 10 Issue 1, p1-1, 1p
- Publication Year :
- 2019
-
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<superscript>+</superscript> T cells have been detected in patients, CD8<superscript>+</superscript> T cells have only been examined to a minor extent. Here we detect CD8<superscript>+</superscript> 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<superscript>+</superscript> 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<superscript>+</superscript> T-cell reactivity combined with HLA-DQB1*06:02 expression is important for NT1 development. Autoreactive T cells are suspected to destroy hypocretin-producing neurons in narcolepsy. Here the authors detect CD8 T cells recognizing narcolepsy-related proteins in healthy individuals and in patients with narcolepsy, and show that the frequency of self-reactive CD8 T cells differs between patients and controls sharing the same HLA-II risk allele. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 20411723
- Volume :
- 10
- Issue :
- 1
- Database :
- Complementary Index
- Journal :
- Nature Communications
- Publication Type :
- Academic Journal
- Accession number :
- 134805956
- Full Text :
- https://doi.org/10.1038/s41467-019-08774-1