Journal article
CD8+ T cells from patients with narcolepsy and healthy controls recognize hypocretin neuron-specific antigens
T-Cells and Cancer, Experimental & Translational Immunology, Department of Health Technology, Technical University of Denmark1
Experimental & Translational Immunology, Department of Health Technology, Technical University of Denmark2
Department of Health Technology, Technical University of Denmark3
Copenhagen University Hospital Herlev and Gentofte4
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.
| Language: | English |
|---|---|
| Publisher: | Nature Publishing Group UK |
| Year: | 2019 |
| Pages: | 837 |
| ISSN: | 20411723 |
| Types: | Journal article |
| DOI: | 10.1038/s41467-019-08774-1 |
| ORCIDs: | Pedersen, Natasja Wulff , Kristensen, Nikolaj Pagh , Bentzen, Amalie Kai , Tamhane, Tripti , Hadrup, Sine Reker , 0000-0002-1831-6746 , 0000-0001-7306-9058 , 0000-0001-6986-5254 and 0000-0002-2515-9451 |
