Autoimmunity to hypocretin and molecular mimicry to flu in type 1 narcolepsy
Identifieur interne : 000220 ( Main/Exploration ); précédent : 000219; suivant : 000221Autoimmunity to hypocretin and molecular mimicry to flu in type 1 narcolepsy
Auteurs : Guo Luo ; Aditya Ambati ; Ling Lin ; Mélodie Bonvalet ; Markku Partinen [Finlande] ; Xuhuai Ji ; Holden Terry Maecker ; Emmanuel Jean-Marie MignotSource :
- Proceedings of the National Academy of Sciences of the United States of America [ 0027-8424 ] ; 2018.
Descripteurs français
- KwdFr :
- Adolescent, Adulte, Adulte d'âge moyen, Auto-immunité (immunologie), Autoantigènes (métabolisme), Chaines bêta des antigènes HLA-DQ, Enfant, Femelle, Grippe humaine (immunologie), Humains, Hémagglutinines, Lymphocytes T CD4+ (immunologie), Mimétisme moléculaire (immunologie), Mâle, Narcolepsie (immunologie), Orexines (génétique), Orexines (immunologie), Orexines (métabolisme), Peptides (génétique), Protéines et peptides de signalisation intracellulaire (génétique), Récepteurs aux antigènes des cellules T (génétique), Sous-type H1N1 du virus de la grippe A (immunologie), Vaccination, Virus de la grippe A (immunologie), Virus de la grippe A (pathogénicité), Épitopes (immunologie).
- MESH :
- génétique : Orexines, Peptides, Protéines et peptides de signalisation intracellulaire, Récepteurs aux antigènes des cellules T.
- immunologie : Auto-immunité, Grippe humaine, Lymphocytes T CD4+, Mimétisme moléculaire, Narcolepsie, Orexines, Sous-type H1N1 du virus de la grippe A, Virus de la grippe A, Épitopes.
- métabolisme : Autoantigènes, Orexines.
- pathogénicité : Virus de la grippe A.
- Adolescent, Adulte, Adulte d'âge moyen, Chaines bêta des antigènes HLA-DQ, Enfant, Femelle, Humains, Hémagglutinines, Mâle, Vaccination.
English descriptors
- KwdEn :
- Adolescent, Adult, Autoantigens (metabolism), Autoimmunity (immunology), CD4-Positive T-Lymphocytes (immunology), Child, Epitopes (immunology), Female, HLA-DQ beta-Chains, Hemagglutinins, Humans, Influenza A Virus, H1N1 Subtype (immunology), Influenza A virus (immunology), Influenza A virus (pathogenicity), Influenza, Human (immunology), Intracellular Signaling Peptides and Proteins (genetics), Male, Middle Aged, Molecular Mimicry (immunology), Narcolepsy (immunology), Orexins (genetics), Orexins (immunology), Orexins (metabolism), Peptides (genetics), Receptors, Antigen, T-Cell (genetics), Vaccination.
- MESH :
- chemical , genetics : Intracellular Signaling Peptides and Proteins, Orexins, Peptides, Receptors, Antigen, T-Cell.
- chemical , immunology : Epitopes, Orexins.
- chemical , metabolism : Autoantigens, Orexins.
- immunology : Autoimmunity, CD4-Positive T-Lymphocytes, Influenza A Virus, H1N1 Subtype, Influenza A virus, Influenza, Human, Molecular Mimicry, Narcolepsy.
- pathogenicity : Influenza A virus.
- Adolescent, Adult, Child, Female, HLA-DQ beta-Chains, Hemagglutinins, Humans, Male, Middle Aged, Vaccination.
Abstract
This work shows that the amidated terminal ends of the secreted hypocretin (HCRT) peptides (HCRTNH2) are autoantigens in type 1 narcolepsy, an autoimmune disorder targeting HCRT neurons. The autoimmune process is usually initiated by influenza A flu infections, and a particular piece of the hemagglutinin (HA) flu protein of the pandemic 2009 H1N1 strain was identified as a likely trigger. This HA epitope has homology with HCRTNH2 and T cells cross-reactive to both epitopes are involved in the autoimmune process by molecular mimicry. Genes associated with narcolepsy mark the particular HLA heterodimer (DQ0602) involved in presentation of these antigens and modulate expression of the specific T cell receptor segments (TRAJ24 and TRBV4-2) involved in T cell receptor recognition of these antigens, suggesting causality.
Url:
DOI: 10.1073/pnas.1818150116
PubMed: 30541895
PubMed Central: 6310865
Affiliations:
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L" first="Ling" last="Lin">Ling Lin</name><affiliation><nlm:aff id="aff1">Center for Sleep Sciences and Medicine,<institution>Stanford University School of Medicine</institution>, Palo Alto,<addr-line>CA</addr-line> 94304;</nlm:aff></affiliation></author><author><name sortKey="Bonvalet, Melodie" sort="Bonvalet, Melodie" uniqKey="Bonvalet M" first="Mélodie" last="Bonvalet">Mélodie Bonvalet</name><affiliation><nlm:aff id="aff1">Center for Sleep Sciences and Medicine,<institution>Stanford University School of Medicine</institution>, Palo Alto,<addr-line>CA</addr-line> 94304;</nlm:aff></affiliation></author><author><name sortKey="Partinen, Markku" sort="Partinen, Markku" uniqKey="Partinen M" first="Markku" last="Partinen">Markku Partinen</name><affiliation wicri:level="1"><nlm:aff id="aff2">Helsinki Sleep Clinic, Vitalmed Research Centre, 00380 Helsinki,<country>Finland</country>;</nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff3">Department of Clinical Neurosciences,<institution>University of Helsinki</institution>, 00100 Helsinki,<country>Finland</country>;</nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Ji, Xuhuai" sort="Ji, Xuhuai" uniqKey="Ji X" first="Xuhuai" last="Ji">Xuhuai Ji</name><affiliation><nlm:aff id="aff4">Immune Monitoring Center, Institute for Immunity, Transplantation, and Infection,<institution>Stanford University School of Medicine</institution>, Palo Alto,<addr-line>CA</addr-line> 94305</nlm:aff></affiliation></author><author><name sortKey="Maecker, Holden Terry" sort="Maecker, Holden Terry" uniqKey="Maecker H" first="Holden Terry" last="Maecker">Holden Terry Maecker</name><affiliation><nlm:aff id="aff4">Immune Monitoring Center, Institute for Immunity, Transplantation, and 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(métabolisme)</term><term>Chaines bêta des antigènes HLA-DQ</term><term>Enfant</term><term>Femelle</term><term>Grippe humaine (immunologie)</term><term>Humains</term><term>Hémagglutinines</term><term>Lymphocytes T CD4+ (immunologie)</term><term>Mimétisme moléculaire (immunologie)</term><term>Mâle</term><term>Narcolepsie (immunologie)</term><term>Orexines (génétique)</term><term>Orexines (immunologie)</term><term>Orexines (métabolisme)</term><term>Peptides (génétique)</term><term>Protéines et peptides de signalisation intracellulaire (génétique)</term><term>Récepteurs aux antigènes des cellules T (génétique)</term><term>Sous-type H1N1 du virus de la grippe A (immunologie)</term><term>Vaccination</term><term>Virus de la grippe A (immunologie)</term><term>Virus de la grippe A (pathogénicité)</term><term>Épitopes (immunologie)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Intracellular Signaling Peptides and Proteins</term><term>Orexins</term><term>Peptides</term><term>Receptors, Antigen, T-Cell</term></keywords><keywords scheme="MESH" type="chemical" qualifier="immunology" xml:lang="en"><term>Epitopes</term><term>Orexins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Autoantigens</term><term>Orexins</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Orexines</term><term>Peptides</term><term>Protéines et peptides de signalisation intracellulaire</term><term>Récepteurs aux antigènes des cellules T</term></keywords><keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Auto-immunité</term><term>Grippe humaine</term><term>Lymphocytes T CD4+</term><term>Mimétisme moléculaire</term><term>Narcolepsie</term><term>Orexines</term><term>Sous-type H1N1 du virus de la grippe A</term><term>Virus de la grippe A</term><term>Épitopes</term></keywords><keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Autoimmunity</term><term>CD4-Positive T-Lymphocytes</term><term>Influenza A Virus, H1N1 Subtype</term><term>Influenza A virus</term><term>Influenza, Human</term><term>Molecular Mimicry</term><term>Narcolepsy</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Autoantigènes</term><term>Orexines</term></keywords><keywords scheme="MESH" qualifier="pathogenicity" xml:lang="en"><term>Influenza A virus</term></keywords><keywords scheme="MESH" qualifier="pathogénicité" xml:lang="fr"><term>Virus de la grippe A</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Adolescent</term><term>Adult</term><term>Child</term><term>Female</term><term>HLA-DQ beta-Chains</term><term>Hemagglutinins</term><term>Humans</term><term>Male</term><term>Middle Aged</term><term>Vaccination</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Adolescent</term><term>Adulte</term><term>Adulte d'âge moyen</term><term>Chaines bêta des antigènes HLA-DQ</term><term>Enfant</term><term>Femelle</term><term>Humains</term><term>Hémagglutinines</term><term>Mâle</term><term>Vaccination</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><title>Significance</title><p>This work shows that the amidated terminal ends of the secreted hypocretin (HCRT) peptides (HCRT<sub>NH2</sub>) are autoantigens in type 1 narcolepsy, an autoimmune disorder targeting HCRT neurons. The autoimmune process is usually initiated by influenza A flu infections, and a particular piece of the hemagglutinin (HA) flu protein of the pandemic 2009 H1N1 strain was identified as a likely trigger. This HA epitope has homology with HCRT<sub>NH2</sub> and T cells cross-reactive to both epitopes are involved in the autoimmune process by molecular mimicry. Genes associated with narcolepsy mark the particular HLA heterodimer (DQ0602) involved in presentation of these antigens and modulate expression of the specific T cell receptor segments (TRAJ24 and TRBV4-2) involved in T cell receptor recognition of these antigens, suggesting causality.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Han, F" uniqKey="Han F">F Han</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Faraco, J" uniqKey="Faraco J">J Faraco</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kornum, Br" uniqKey="Kornum B">BR Kornum</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hor, H" uniqKey="Hor H">H Hor</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hallmayer, J" uniqKey="Hallmayer J">J Hallmayer</name></author></analytic></biblStruct><biblStruct><analytic><author><name 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Risnes</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Han, F" uniqKey="Han F">F Han</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cushing, A" uniqKey="Cushing A">A Cushing</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Montplaisir, J" uniqKey="Montplaisir J">J Montplaisir</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="La Gruta, Nl" uniqKey="La Gruta N">NL La Gruta</name></author><author><name sortKey="Gras, S" uniqKey="Gras S">S Gras</name></author><author><name sortKey="Daley, Sr" uniqKey="Daley S">SR Daley</name></author><author><name sortKey="Thomas, Pg" uniqKey="Thomas P">PG Thomas</name></author><author><name sortKey="Rossjohn, J" uniqKey="Rossjohn J">J Rossjohn</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hahn, M" uniqKey="Hahn M">M Hahn</name></author><author><name sortKey="Nicholson, Mj" uniqKey="Nicholson M">MJ Nicholson</name></author><author><name sortKey="Pyrdol, J" uniqKey="Pyrdol J">J Pyrdol</name></author><author><name sortKey="Wucherpfennig, Kw" uniqKey="Wucherpfennig K">KW Wucherpfennig</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Riley, Tp" uniqKey="Riley T">TP Riley</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>Finlande</li></country></list><tree><noCountry><name sortKey="Ambati, Aditya" sort="Ambati, Aditya" uniqKey="Ambati A" first="Aditya" last="Ambati">Aditya Ambati</name><name sortKey="Bonvalet, Melodie" sort="Bonvalet, Melodie" uniqKey="Bonvalet M" first="Mélodie" last="Bonvalet">Mélodie Bonvalet</name><name sortKey="Ji, Xuhuai" sort="Ji, Xuhuai" uniqKey="Ji X" first="Xuhuai" last="Ji">Xuhuai Ji</name><name sortKey="Lin, Ling" sort="Lin, Ling" uniqKey="Lin L" first="Ling" last="Lin">Ling Lin</name><name sortKey="Luo, Guo" sort="Luo, Guo" uniqKey="Luo G" first="Guo" last="Luo">Guo Luo</name><name sortKey="Maecker, Holden Terry" sort="Maecker, Holden Terry" uniqKey="Maecker H" first="Holden Terry" last="Maecker">Holden Terry Maecker</name><name sortKey="Mignot, Emmanuel Jean Marie" sort="Mignot, Emmanuel Jean Marie" uniqKey="Mignot E" first="Emmanuel Jean-Marie" last="Mignot">Emmanuel Jean-Marie Mignot</name></noCountry><country name="Finlande"><noRegion><name sortKey="Partinen, Markku" sort="Partinen, Markku" uniqKey="Partinen M" first="Markku" last="Partinen">Markku Partinen</name></noRegion><name sortKey="Partinen, Markku" sort="Partinen, Markku" uniqKey="Partinen M" first="Markku" last="Partinen">Markku Partinen</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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