{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T11:14:06Z","timestamp":1768475646652,"version":"3.49.0"},"reference-count":67,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2021,6,29]],"date-time":"2021-06-29T00:00:00Z","timestamp":1624924800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004564","name":"Ministarstvo Prosvete, Nauke i Tehnolo\u0161kog Razvoja","doi-asserted-by":"publisher","award":["451-03-9\/2021-14\/200178"],"award-info":[{"award-number":["451-03-9\/2021-14\/200178"]}],"id":[{"id":"10.13039\/501100004564","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Autoimmune diseases, often triggered by infection, affect ~5% of the worldwide population. Rheumatoid Arthritis (RA)\u2013a painful condition characterized by the chronic inflammation of joints\u2014comprises up to 20% of known autoimmune pathologies, with the tendency of increasing prevalence. Molecular mimicry is recognized as the leading mechanism underlying infection-mediated autoimmunity, which assumes sequence similarity between microbial and self-peptides driving the activation of autoreactive lymphocytes. T lymphocytes are leading immune cells in the RA-development. Therefore, deeper understanding of the capacity of microorganisms (both pathogens and commensals) to trigger autoreactive T cells is needed, calling for more systematic approaches. In the present study, we address this problem through a comprehensive immunoinformatics analysis of experimentally determined RA-related T cell epitopes against the proteomes of Bacteria, Fungi, and Viruses, to identify the scope of organisms providing homologous antigenic peptide determinants. By this, initial homology screening was complemented with <jats:italic>de novo<\/jats:italic> T cell epitope prediction and another round of homology search, to enable: <jats:italic>i<\/jats:italic>) the confirmation of homologous microbial peptides as T cell epitopes based on the predicted binding affinity to RA-related HLA polymorphisms; <jats:italic>ii<\/jats:italic>) sequence similarity inference for top <jats:italic>de novo<\/jats:italic> T cell epitope predictions to the RA-related autoantigens to reveal the robustness of RA-triggering capacity for identified (micro\/myco)organisms. Our study reveals a much larger repertoire of candidate RA-triggering organisms, than previously recognized, providing insights into the underestimated role of Fungi in autoimmunity and the possibility of a more direct involvement of bacterial commensals in RA-pathology. Finally, our study pinpoints Endoplasmic reticulum chaperone BiP as the most potent (most likely mimicked) RA-related autoantigen, opening an avenue for identifying the most potent autoantigens in a variety of different autoimmune pathologies, with possible implications in the design of next-generation therapeutics aiming to induce self-tolerance by affecting highly reactive autoantigens.<\/jats:p>","DOI":"10.1371\/journal.pone.0253918","type":"journal-article","created":{"date-parts":[[2021,6,29]],"date-time":"2021-06-29T17:39:52Z","timestamp":1624988392000},"page":"e0253918","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":20,"title":["Mining the capacity of human-associated microorganisms to trigger rheumatoid arthritis\u2014A systematic immunoinformatics analysis of T cell epitopes"],"prefix":"10.1371","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3041-1850","authenticated-orcid":true,"given":"Jelena","family":"Repac","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marija","family":"Mandi\u0107","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tanja","family":"Luni\u0107","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9910-2741","authenticated-orcid":true,"given":"Bojan","family":"Bo\u017ei\u0107","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1238-1731","authenticated-orcid":true,"given":"Biljana","family":"Bo\u017ei\u0107 Nedeljkovi\u0107","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2021,6,29]]},"reference":[{"issue":"4","key":"pone.0253918.ref001","doi-asserted-by":"crossref","first-page":"151","DOI":"10.12691\/ijcd-3-4-8","article-title":"The world incidence and prevalence of autoimmune diseases is increasing","volume":"3","author":"A Lerner","year":"2015","journal-title":"Int J Celiac Dis"},{"issue":"6","key":"pone.0253918.ref002","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1111\/j.1365-2036.1987.tb00652.x","article-title":"The effect of two \u03b12-adrenoreceptor agonists and an antagonist on gastric emptying and mouth to caecum transit time in humans","volume":"1","author":"A Baxter","year":"1987","journal-title":"Aliment Pharmacol Ther"},{"issue":"2","key":"pone.0253918.ref003","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1016\/j.berh.2018.10.005","article-title":"Update on the epidemiology, risk factors, and disease outcomes of rheumatoid arthritis","volume":"32","author":"D van der Woude","year":"2018","journal-title":"Best Pract Res Clin Rheumatol"},{"issue":"10","key":"pone.0253918.ref004","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1038\/nrrheum.2011.121","article-title":"The microbiome and rheumatoid arthritis","volume":"7","author":"JU Scher","year":"2011","journal-title":"Nature Reviews Rheumatology"},{"issue":"10","key":"pone.0253918.ref005","doi-asserted-by":"crossref","first-page":"161","DOI":"10.3390\/cells7100161","article-title":"Pathogenic role of immune cells in rheumatoid arthritis: implications in clinical treatment and biomarker development","volume":"7","author":"H-Y Yap","year":"2018","journal-title":"Cells"},{"issue":"1","key":"pone.0253918.ref006","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.1365-2249.2008.03834.x","article-title":"The role of infections in autoimmune disease","volume":"155","author":"A Ercolini","year":"2009","journal-title":"Clin Exp Immunol"},{"key":"pone.0253918.ref007","first-page":"1","article-title":"Molecular mimicry, microbial infection, and autoimmune disease: evolution of the concept","author":"M Oldstone","year":"2005","journal-title":"Molecular Mimicry: Infection-Inducing Autoimmune Disease"},{"issue":"1","key":"pone.0253918.ref008","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":"MF Cusick","year":"2012","journal-title":"Clin Rev Allergy Immunol"},{"issue":"3","key":"pone.0253918.ref009","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1007\/s12016-015-8493-8","article-title":"Environmental basis of autoimmunity","volume":"50","author":"A Floreani","year":"2016","journal-title":"Clin Rev Allergy Immunol"},{"issue":"6","key":"pone.0253918.ref010","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1002\/ana.21141","article-title":"Environmental risk factors for multiple sclerosis. 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