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Using in silico homology searches, we identified two viral epitopes (evglekl and vtgtqgt) within the TBEV E protein that share sequence identity with fragments of the human proteins DNAH7 and CSMD2. Antibodies against these epitopes were detected in the plasma of a subset of patients after natural TBEV infection. Notably, no such antibodies were found in recipients of the Tick-E-Vac vaccine, indicating that the current vaccine does not induce cross-reactive humoral responses to these epitopes. Further computational analysis predicted that these epitopes could be presented by HLA class II molecules (alleles DRB1*09:01 and DRB1*07:01), which are known to be associated with autoimmune pathologies. Molecular dynamics simulations confirmed stable binding of the peptides within the HLA grooves, with favorable binding energies. These findings suggest a possible involvement of T-helper cells in the autoreactive process. Natural TBEV infection can give rise to antibodies against epitopes homologous to human proteins, particularly in genetically predisposed hosts. While such homology alone does not predict the onset of autoimmune disease, it represents a risk factor.<\/jats:p>","DOI":"10.3390\/ijms27114745","type":"journal-article","created":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T11:57:44Z","timestamp":1779710264000},"page":"4745","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Molecular Mimicry by the Tick-Borne Encephalitis Virus E Protein: A Hidden Link to Autoimmunity"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1270-7164","authenticated-orcid":false,"given":"Anna M.","family":"Timofeeva","sequence":"first","affiliation":[{"name":"SB RAS Institute of Chemical Biology and Fundamental Medicine, 630090 Novosibirsk, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6972-9068","authenticated-orcid":false,"given":"Ksenia S.","family":"Aulova","sequence":"additional","affiliation":[{"name":"SB RAS Institute of Chemical Biology and Fundamental Medicine, 630090 Novosibirsk, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yana S.","family":"Ulyanova","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Novosibirsk State Medical University, 630091 Novosibirsk, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark M.","family":"Melamud","sequence":"additional","affiliation":[{"name":"SB RAS Institute of Chemical Biology and Fundamental Medicine, 630090 Novosibirsk, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4812-3037","authenticated-orcid":false,"given":"Sergey G.","family":"Arkhipov","sequence":"additional","affiliation":[{"name":"SRF \u201cSKIF\u201d, 630559 Koltsovo, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena I.","family":"Krasnova","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Novosibirsk State Medical University, 630091 Novosibirsk, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgy A.","family":"Nevinsky","sequence":"additional","affiliation":[{"name":"SB RAS Institute of Chemical Biology and Fundamental Medicine, 630090 Novosibirsk, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Rar, V., Chicherina, G., Igolkina, Y., Fedorets, V., Epikhina, T., and Tikunova, N. 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