{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T20:21:25Z","timestamp":1790281285179,"version":"4.1.0"},"reference-count":210,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2025,9,10]],"date-time":"2025-09-10T00:00:00Z","timestamp":1757462400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006769","name":"Russian Science Foundation","doi-asserted-by":"publisher","award":["25-15-00010"],"award-info":[{"award-number":["25-15-00010"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>This study investigated the role of molecular mimicry in the context of autoimmunity associated with viral infection, using SARS-CoV-2 as a model system. A bioinformatic analysis was performed to identify sequence homologies between the SARS-CoV-2 Spike (S) protein and the human proteome, with a specific focus on immunogenic regions to assess potential cross-reactivity. The analysis revealed homologous regions between the viral S protein and several human proteins, including DAAM2, CHL1, HAVR2\/TIM3, FSTL1, FHOD3, MYO18A, EMILIN3, LAMP1, and \u03b1ENaC, which are predicted to be recognizable by B-cell receptors. Such recognition could potentially lead to the production of autoreactive antibodies, which can contribute to the development of autoimmune diseases. Furthermore, the study examined potential autoreactive CD4+ T-cell responses to human protein autoepitopes that could be presented by HLA class II molecules. Several HLA class II genetic variants were computationally associated with a higher likelihood of cross-reactive immune reactions following COVID-19, including HLA-DPA1*01:03\/DPB1*02:01, HLA-DPA1*02:01\/DPB1*01:01, HLA-DPA1*02:01\/DPB1*05:01, HLA-DPA1*02:01\/DPB1*14:01, HLA-DQA1*01:02\/DQB1*06:02, HLA-DRB1*04:01, HLA-DRB1*04:05, HLA-DRB1*07:01, and HLA-DRB1*15:01. Additionally, seven T helper cell autoepitopes (YSEILDKYFKNFDNG, ERTRFQTLLNELDRS, AERTRFQTLLNELDR, RERKVEAEVQAIQEQ, NAINIGLTVLPPPRT, PQSAVYSTGSNGILL, TIRIGIYIGAGICAG) were identified that could be implicated in autoimmune T-cell responses through presentation by class II HLA molecules. These findings highlight the utility of viral B- and T-cell epitope prediction for investigating molecular mimicry as a possible mechanism in virus-associated autoimmunity.<\/jats:p>","DOI":"10.3390\/ijms26188793","type":"journal-article","created":{"date-parts":[[2025,9,10]],"date-time":"2025-09-10T10:27:12Z","timestamp":1757500032000},"page":"8793","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["SARS-CoV-2 Spike Protein and Molecular Mimicry: An Immunoinformatic Screen for Cross-Reactive Autoantigen Candidates"],"prefix":"10.3390","volume":"26","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, Novosibirsk 630090, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6972-9068","authenticated-orcid":false,"given":"Kseniya S.","family":"Aulova","sequence":"additional","affiliation":[{"name":"SB RAS Institute of Chemical Biology and Fundamental Medicine, Novosibirsk 630090, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-2185-3515","authenticated-orcid":false,"given":"Egor A.","family":"Mustaev","sequence":"additional","affiliation":[{"name":"SRF \u201cSKIF\u201d, Koltsovo 630559, Russia"},{"name":"Department of Natural Sciences, Novosibirsk State University, Novosibirsk 630090, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4988-8923","authenticated-orcid":false,"given":"Georgy A.","family":"Nevinsky","sequence":"additional","affiliation":[{"name":"SB RAS Institute of Chemical Biology and Fundamental Medicine, Novosibirsk 630090, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1255","DOI":"10.1096\/fasebj.12.13.1255","article-title":"Molecular mimicry and immune-mediated diseases","volume":"12","author":"Oldstone","year":"1998","journal-title":"FASEB J."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1007\/s12016-011-8294-7","article-title":"Molecular Mimicry as a Mechanism of Autoimmune Disease","volume":"42","author":"Cusick","year":"2011","journal-title":"Clin. 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