T cell reactivity to regulatory factor X4 in type 1 narcolepsy

Abstract Type 1 narcolepsy is strongly (98%) associated with human leukocyte antigen (HLA) class II DQA1*01:02/DQB1*06:02 (DQ0602) and highly associated with T cell receptor (TCR) alpha locus polymorphism as well as other immune regulatory loci. Increased incidence of narcolepsy was detected followi...

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Autores principales:	Guo Luo, Selina Yogeshwar, Ling Lin, Emmanuel Jean-Marie Mignot
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/068c99f5a1b243e090a7790584f5f145
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spelling	oai:doaj.org-article:068c99f5a1b243e090a7790584f5f1452021-12-02T14:15:53ZT cell reactivity to regulatory factor X4 in type 1 narcolepsy10.1038/s41598-021-87481-82045-2322https://doaj.org/article/068c99f5a1b243e090a7790584f5f1452021-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-87481-8https://doaj.org/toc/2045-2322Abstract Type 1 narcolepsy is strongly (98%) associated with human leukocyte antigen (HLA) class II DQA101:02/DQB106:02 (DQ0602) and highly associated with T cell receptor (TCR) alpha locus polymorphism as well as other immune regulatory loci. Increased incidence of narcolepsy was detected following the 2009 H1N1 pandemic and linked to Pandemrix vaccination, strongly supporting that narcolepsy is an autoimmune disorder. Although recent results suggest CD4+ T cell reactivity to neuropeptide hypocretin/orexin and cross-reactive flu peptide is involved, identification of other autoantigens has remained elusive. Here we study whether autoimmunity directed against Regulatory Factor X4 (RFX4), a protein co-localized with hypocretin, is involved in some cases of narcolepsy. Studying human serum, we found that autoantibodies against RFX4 were rare. Using RFX4 peptides bound to DQ0602 tetramers, antigen RFX4-86, -95, and -60 specific human CD4+ T cells were detected in 4/10 patients and 2 unaffected siblings, but not in others. Following culture with each cognate peptide, enriched autoreactive TCRαβ clones were isolated by single-cell sorting and TCR sequenced. Homologous clones bearing TRBV4-2 and recognizing RFX4-86 in patients and one twin control of patient were identified. These results suggest the involvement of RFX4 CD4+ T cell autoreactivity in some cases of narcolepsy, but also in healthy donors.Guo LuoSelina YogeshwarLing LinEmmanuel Jean-Marie MignotNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Guo Luo Selina Yogeshwar Ling Lin Emmanuel Jean-Marie Mignot T cell reactivity to regulatory factor X4 in type 1 narcolepsy
description	Abstract Type 1 narcolepsy is strongly (98%) associated with human leukocyte antigen (HLA) class II DQA101:02/DQB106:02 (DQ0602) and highly associated with T cell receptor (TCR) alpha locus polymorphism as well as other immune regulatory loci. Increased incidence of narcolepsy was detected following the 2009 H1N1 pandemic and linked to Pandemrix vaccination, strongly supporting that narcolepsy is an autoimmune disorder. Although recent results suggest CD4+ T cell reactivity to neuropeptide hypocretin/orexin and cross-reactive flu peptide is involved, identification of other autoantigens has remained elusive. Here we study whether autoimmunity directed against Regulatory Factor X4 (RFX4), a protein co-localized with hypocretin, is involved in some cases of narcolepsy. Studying human serum, we found that autoantibodies against RFX4 were rare. Using RFX4 peptides bound to DQ0602 tetramers, antigen RFX4-86, -95, and -60 specific human CD4+ T cells were detected in 4/10 patients and 2 unaffected siblings, but not in others. Following culture with each cognate peptide, enriched autoreactive TCRαβ clones were isolated by single-cell sorting and TCR sequenced. Homologous clones bearing TRBV4-2 and recognizing RFX4-86 in patients and one twin control of patient were identified. These results suggest the involvement of RFX4 CD4+ T cell autoreactivity in some cases of narcolepsy, but also in healthy donors.
format	article
author	Guo Luo Selina Yogeshwar Ling Lin Emmanuel Jean-Marie Mignot
author_facet	Guo Luo Selina Yogeshwar Ling Lin Emmanuel Jean-Marie Mignot
author_sort	Guo Luo
title	T cell reactivity to regulatory factor X4 in type 1 narcolepsy
title_short	T cell reactivity to regulatory factor X4 in type 1 narcolepsy
title_full	T cell reactivity to regulatory factor X4 in type 1 narcolepsy
title_fullStr	T cell reactivity to regulatory factor X4 in type 1 narcolepsy
title_full_unstemmed	T cell reactivity to regulatory factor X4 in type 1 narcolepsy
title_sort	t cell reactivity to regulatory factor x4 in type 1 narcolepsy
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/068c99f5a1b243e090a7790584f5f145
work_keys_str_mv	AT guoluo tcellreactivitytoregulatoryfactorx4intype1narcolepsy AT selinayogeshwar tcellreactivitytoregulatoryfactorx4intype1narcolepsy AT linglin tcellreactivitytoregulatoryfactorx4intype1narcolepsy AT emmanueljeanmariemignot tcellreactivitytoregulatoryfactorx4intype1narcolepsy
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T cell reactivity to regulatory factor X4 in type 1 narcolepsy

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