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

Nat Commun. 2019 Feb 19;10(1):837. doi: 10.1038/s41467-019-08774-1.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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
  • Narcolepsy / immunology*
  • Neurons / metabolism
  • Orexins / immunology*
  • Orexins / metabolism
  • Peptides / immunology*

Substances

  • HLA-DQ beta-Chains
  • HLA-DQB1 antigen
  • Orexins
  • Peptides