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

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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.

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Pedersen, N. W., Holm, A., Kristensen, N. P., Bjerregaard, A. M., Bentzen, A. K., Marquard, A. M., … Kornum, B. R. (2019). CD8 + T cells from patients with narcolepsy and healthy controls recognize hypocretin neuron-specific antigens. Nature Communications, 10(1). https://doi.org/10.1038/s41467-019-08774-1

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