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In vivo clonal expansion and phenotypes of hypocretin-specific CD4+ T cells in narcolepsy patients and controls

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  • Wei Jiang
  • James R Birtley
  • Shu-Chen Hung
  • Weiqi Wang
  • Shin-Heng Chiou
  • Claudia Macaubas
  • Birgitte Kornum
  • Lu Tian
  • Huang Huang
  • Lital Adler
  • Grant Weaver
  • Liying Lu
  • Alexandra Ilstad-Minnihan
  • Sriram Somasundaram
  • Sashi Ayyangar
  • Mark M Davis
  • Lawrence J Stern
  • Elizabeth D Mellins
Vis graf over relationer

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 α (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+ TCRαβ clonotypes encoded by identical α/β 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.

OriginalsprogEngelsk
TidsskriftNature Communications
Vol/bind10
Udgave nummer1
Sider (fra-til)5247
ISSN2041-1723
DOI
StatusUdgivet - 20 nov. 2019

ID: 59153837