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

A. Vuorela, T. L. Freitag (), K. Leskinen, H. Pessa, T. Härkönen, I. Stracenski, T. Kirjavainen, P. Olsen, O. Saarenpää-Heikkilä, J. Ilonen, M. Knip, A. Vaheri, M. Partinen, P. Saavalainen, S. Meri and O. Vaarala
Additional contact information
A. Vuorela: University of Helsinki
T. L. Freitag: University of Helsinki
K. Leskinen: University of Helsinki
H. Pessa: University of Helsinki
T. Härkönen: University of Helsinki
I. Stracenski: University of Helsinki
T. Kirjavainen: University of Helsinki, and Helsinki University Hospital
P. Olsen: Oulu University Hospital
O. Saarenpää-Heikkilä: Tampere University Hospital
J. Ilonen: University of Turku
M. Knip: University of Helsinki
A. Vaheri: University of Helsinki
M. Partinen: University of Helsinki
P. Saavalainen: University of Helsinki
S. Meri: University of Helsinki
O. Vaarala: University of Helsinki

Nature Communications, 2021, vol. 12, issue 1, 1-17

Abstract: 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.

Date: 2021
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DOI: 10.1038/s41467-021-22637-8

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