Enhanced influenza A H1N1 T cell epitope recognition and cross-reactivity to protein-O-mannosyltransferase 1 in Pandemrix-associated narcolepsy type 1
Vuorela, A.; Freitag, T. L.; Leskinen, K.; Pessa, H.; Härkönen, T.; Stracenski, I.; Kirjavainen, T.; Olsen, P.; Saarenpää-Heikkilä, O.; Ilonen, J.; Knip, M.; Vaheri, A.; Partinen, M.; Saavalainen, P.; Meri, S.; Vaarala, O. (2021-04)
Vuorela, A.
Freitag, T. L.
Leskinen, K.
Pessa, H.
Härkönen, T.
Stracenski, I.
Kirjavainen, T.
Olsen, P.
Saarenpää-Heikkilä, O.
Ilonen, J.
Knip, M.
Vaheri, A.
Partinen, M.
Saavalainen, P.
Meri, S.
Vaarala, O.
04 / 2021
2283
Julkaisun pysyvä osoite on
https://urn.fi/URN:NBN:fi:tuni-202105205226
https://urn.fi/URN:NBN:fi:tuni-202105205226
Kuvaus
Peer reviewed
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.
Kokoelmat
- TUNICRIS-julkaisut [16983]