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Absence of autoreactive CD4+ T-cells targeting HLA-DQA1*01:02/DQB1*06:02 restricted hypocretin/orexin epitopes in narcolepsy type 1 when detected by EliSpot

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Narcolepsy type 1, a neurological sleep disorder strongly associated with Human Leukocyte Antigen (HLA-)DQB1*06:02, is caused by the loss of hypothalamic neurons producing the wake-promoting neuropeptide hypocretin (hcrt, also known as orexin). This loss is believed to be caused by an autoimmune reaction. To test whether hcrt itself could be a possible target in the autoimmune attack, CD4+ T-cell reactivity towards six different 15-mer peptides from prepro-hypocretin with high predicted affinity to the DQA1*01:02/DQB1*06:02 MHC class II dimer was tested using EliSpot in a cohort of 22 narcolepsy patients with low CSF hcrt levels, and 23 DQB1*06:02 positive healthy controls. Our ELISpot assay had a detection limit of 1:10,000 cells. We present data showing that autoreactive CD4+ T-cells targeting epitopes from the hcrt precursor in the context of MHC-DQA1*01:02/DQB1*06:02 are either not present or present in a frequency is <1:10,000 among peripheral CD4+ T-cells from narcolepsy type 1 patients.

Original languageEnglish
JournalJournal of Neuroimmunology
Volume309
Pages (from-to)7-11
Number of pages5
ISSN0165-5728
DOIs
Publication statusPublished - 15 Aug 2017

    Research areas

  • Adolescent, Adult, Amino Acid Sequence, CD4-Positive T-Lymphocytes, Child, Cohort Studies, Enzyme-Linked Immunospot Assay, Epitopes, Female, HLA-DQ alpha-Chains, HLA-DQ beta-Chains, Humans, Male, Middle Aged, Narcolepsy, Orexins, Young Adult, Journal Article

ID: 52121057