UMMS Affiliation

Department of Pathology

Publication Date

2019-11-20

Document Type

Article

Disciplines

Amino Acids, Peptides, and Proteins | Biological Phenomena, Cell Phenomena, and Immunity | Genetic Phenomena | Hemic and Immune Systems | Immunopathology | Mental Disorders | Nervous System Diseases | Neuroscience and Neurobiology | Pathological Conditions, Signs and Symptoms | Pathology

Abstract

Individuals with narcolepsy suffer from abnormal sleep patterns due to loss of neurons that uniquely supply hypocretin (HCRT). Previous studies found associations of narcolepsy with the human leukocyte antigen (HLA)-DQ6 allele and T-cell receptor alpha (TRA) J24 gene segment and also suggested that in vitro-stimulated T cells can target HCRT. Here, we present evidence of in vivo expansion of DQ6-HCRT tetramer(+)/TRAJ24(+)/CD4(+) T cells in DQ6(+) individuals with and without narcolepsy. We identify related TRAJ24(+) TCRalphabeta clonotypes encoded by identical alpha/beta gene regions from two patients and two controls. TRAJ24-G allele(+) clonotypes only expand in the two patients, whereas a TRAJ24-C allele(+) clonotype expands in a control. A representative tetramer(+)/G-allele(+) TCR shows signaling reactivity to the epitope HCRT87-97. Clonally expanded G-allele(+) T cells exhibit an unconventional effector phenotype. Our analysis of in vivo expansion of HCRT-reactive TRAJ24(+) cells opens an avenue for further investigation of the autoimmune contribution to narcolepsy development.

Keywords

Autoimmune diseases, Neuroimmunology, Peripheral tolerance, Sleep disorders, T-cell receptor

Rights and Permissions

© The Author(s) 2019. Open Access: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/ licenses/by/4.0/.

DOI of Published Version

10.1038/s41467-019-13234-x

Source

Nat Commun. 2019 Nov 20;10(1):5247. doi: 10.1038/s41467-019-13234-x. Link to article on publisher's site

Journal/Book/Conference Title

Nature communications

Comments

Full author list omitted for brevity. For the full list of authors, see article.

Related Resources

Link to Article in PubMed

PubMed ID

31748512

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

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