UMMS Affiliation

Department of Pathology

Publication Date


Document Type



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


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.


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

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DOI of Published Version



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


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

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Creative Commons License

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