A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä

Enhanced influenza A H1N1 T cell epitope recognition and cross-reactivity to protein-O-mannosyltransferase 1 in Pandemrix-associated narcolepsy type 1




TekijätVuorela A, Freitag TL, Leskinen K, Pessa H, Härkönen T, Stracenski I, Kirjavainen T, Olsen P, Saarenpää-Heikkilä O, Ilonen Jorma, Knip M, Vaheri A, Partinen M, Saavalainen P, Meri S, Vaarala O

KustantajaNATURE RESEARCH

Julkaisuvuosi2021

JournalNature Communications

Lehden akronyymiNAT COMMUN

Artikkelin numeroARTN 2283

Vuosikerta12

Numero1

Sivujen määrä17

ISSN2041-1723

eISSN2041-1723

DOIhttps://doi.org/10.1038/s41467-021-22637-8

Verkko-osoitehttps://www.nature.com/articles/s41467-021-22637-8

Rinnakkaistallenteen osoitehttps://research.utu.fi/converis/portal/detail/Publication/56057832


Tiivistelmä

Narcolepsy type 1 (NT1) is a chronic neurological disorder having a strong association with HLA-DQB1*0602, thereby suggesting an immunological origin. Increased risk of NT1 has been reported among children or adolescents vaccinated with AS03 adjuvant-supplemented pandemic H1N1 influenza A vaccine, Pandemrix. Here we show that pediatric Pandemrix-associated NT1 patients have enhanced T-cell immunity against the viral epitopes, neuraminidase 175-189 (NA175-189) and nucleoprotein 214-228 (NP214-228), but also respond to a NA175-189-mimic, brain self-epitope, protein-O-mannosyltransferase 1 (POMT1675-689). A pathogenic role of influenza virus-specific T-cells and T-cell cross-reactivity in NT1 are supported by the up-regulation of IFN-γ, perforin 1 and granzyme B, and by the converging selection of T-cell receptor TRAV10/TRAJ17 and TRAV10/TRAJ24 clonotypes, in response to stimulation either with peptide NA175-189 or POMT1675-689. Moreover, anti-POMT1 serum autoantibodies are increased in Pandemrix-vaccinated children or adolescents. These results thus identify POMT1 as a potential autoantigen recognized by T- and B-cells in NT1.


Ladattava julkaisu

This is an electronic reprint of the original article.
This reprint may differ from the original in pagination and typographic detail. Please cite the original version.





Last updated on 2024-26-11 at 21:45