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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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Harvard

Jiang, W, Birtley, JR, Hung, S-C, Wang, W, Chiou, S-H, Macaubas, C, Kornum, B, Tian, L, Huang, H, Adler, L, Weaver, G, Lu, L, Ilstad-Minnihan, A, Somasundaram, S, Ayyangar, S, Davis, MM, Stern, LJ & Mellins, ED 2019, 'In vivo clonal expansion and phenotypes of hypocretin-specific CD4+ T cells in narcolepsy patients and controls', Nature Communications, bind 10, nr. 1, s. 5247. https://doi.org/10.1038/s41467-019-13234-x

APA

Jiang, W., Birtley, J. R., Hung, S-C., Wang, W., Chiou, S-H., Macaubas, C., Kornum, B., Tian, L., Huang, H., Adler, L., Weaver, G., Lu, L., Ilstad-Minnihan, A., Somasundaram, S., Ayyangar, S., Davis, M. M., Stern, L. J., & Mellins, E. D. (2019). In vivo clonal expansion and phenotypes of hypocretin-specific CD4+ T cells in narcolepsy patients and controls. Nature Communications, 10(1), 5247. https://doi.org/10.1038/s41467-019-13234-x

CBE

Jiang W, Birtley JR, Hung S-C, Wang W, Chiou S-H, Macaubas C, Kornum B, Tian L, Huang H, Adler L, Weaver G, Lu L, Ilstad-Minnihan A, Somasundaram S, Ayyangar S, Davis MM, Stern LJ, Mellins ED. 2019. In vivo clonal expansion and phenotypes of hypocretin-specific CD4+ T cells in narcolepsy patients and controls. Nature Communications. 10(1):5247. https://doi.org/10.1038/s41467-019-13234-x

MLA

Vancouver

Author

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 vivo clonal expansion and phenotypes of hypocretin-specific CD4+ T cells in narcolepsy patients and controls. I: Nature Communications. 2019 ; Bind 10, Nr. 1. s. 5247.

Bibtex

@article{b46c8574304e4d2c83b051f920d5227e,
title = "In vivo clonal expansion and phenotypes of hypocretin-specific CD4+ T cells in narcolepsy patients and controls",
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 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.",
author = "Wei Jiang and Birtley, {James R} and Shu-Chen Hung and Weiqi Wang and Shin-Heng Chiou and Claudia Macaubas and Birgitte Kornum and Lu Tian and Huang Huang and Lital Adler and Grant Weaver and Liying Lu and Alexandra Ilstad-Minnihan and Sriram Somasundaram and Sashi Ayyangar and Davis, {Mark M} and Stern, {Lawrence J} and Mellins, {Elizabeth D}",
year = "2019",
month = nov,
day = "20",
doi = "10.1038/s41467-019-13234-x",
language = "English",
volume = "10",
pages = "5247",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",

}

RIS

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 - 2019/11/20

Y1 - 2019/11/20

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

VL - 10

SP - 5247

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

IS - 1

ER -

ID: 59153837