In vivo clonal expansion and phenotypes of hypocretin-specific CD4+ T cells in narcolepsy patients and controls
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In vivo clonal expansion and phenotypes of hypocretin-specific CD4+ T cells in narcolepsy patients and controls. / Jiang, Wei; Birtley, James R.; Hung, Shu Chen; Wang, Weiqi; Chiou, Shin Heng; Macaubas, Claudia; Kornum, Birgitte; Tian, Lu; Huang, Huang; Adler, Lital; Weaver, Grant; Lu, Liying; Ilstad-Minnihan, Alexandra; Somasundaram, Sriram; Ayyangar, Sashi; Davis, Mark M.; Stern, Lawrence J.; Mellins, Elizabeth D.
In: Nature Communications, Vol. 10, No. 1, 5247, 2019.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - In vivo clonal expansion and phenotypes of hypocretin-specific CD4+ T cells in narcolepsy patients and controls
AU - Jiang, Wei
AU - Birtley, James R.
AU - Hung, Shu Chen
AU - Wang, Weiqi
AU - Chiou, Shin Heng
AU - Macaubas, Claudia
AU - Kornum, Birgitte
AU - Tian, Lu
AU - Huang, Huang
AU - Adler, Lital
AU - Weaver, Grant
AU - Lu, Liying
AU - Ilstad-Minnihan, Alexandra
AU - Somasundaram, Sriram
AU - Ayyangar, Sashi
AU - Davis, Mark M.
AU - Stern, Lawrence J.
AU - Mellins, Elizabeth D.
PY - 2019
Y1 - 2019
N2 - 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.
AB - 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.
U2 - 10.1038/s41467-019-13234-x
DO - 10.1038/s41467-019-13234-x
M3 - Journal article
C2 - 31748512
AN - SCOPUS:85075347619
VL - 10
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
IS - 1
M1 - 5247
ER -
ID: 236510158