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Nat.Com. Enhanced influenza A H1N1 T cell epitope recognition and cross-reactivity to protein-O-mannosyltransferase 1 in Pandemrix-associated narcolep

tetano

tetano

Editor, Senior Moderator
Enhanced influenza A H1N1 T cell epitope recognition and cross-reactivity to protein-O-mannosyltransferase 1 in Pandemrix-associated narcolepsy type 1
Nature Communications volume 12, Article number: 2283 (2021) Cite this article
Subjects


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 (NA[SUB]175?189[/SUB]) and nucleoprotein 214?228 (NP[SUB]214?228[/SUB]), but also respond to a NA[SUB]175?189[/SUB]-mimic, brain self-epitope, protein-O-mannosyltransferase 1 (POMT1[SUB]675?689[/SUB]). A pathogenic role of influenza virus-specific T-cells and T-cell cross-reactivity in NT1 are supported by the up-regulation of IFN-?, 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 NA[SUB]175?189[/SUB] or POMT1[SUB]675?689[/SUB]. 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.



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