A1 Refereed original research article in a scientific journal

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




AuthorsVuorela 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

PublisherNATURE RESEARCH

Publication year2021

JournalNature Communications

Journal acronymNAT COMMUN

Article numberARTN 2283

Volume12

Issue1

Number of pages17

ISSN2041-1723

eISSN2041-1723

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

Web address https://www.nature.com/articles/s41467-021-22637-8(external)

Self-archived copy’s web addresshttps://research.utu.fi/converis/portal/detail/Publication/56057832(external)


Abstract

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.


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