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.

SUBMITTER: Pedersen NW 

PROVIDER: S-EPMC6381094 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature