{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T05:45:07Z","timestamp":1790401507143,"version":"4.1.0"},"reference-count":67,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,4,15]],"date-time":"2021-04-15T00:00:00Z","timestamp":1618444800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000781","name":"European Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000781","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Increasing evidence suggests that post-translational peptide splicing can play a role in the immune response under pathological conditions. This seems to be particularly relevant in Type 1 Diabetes (T1D) since post-translationally spliced epitopes derived from T1D-associated antigens have been identified among those peptides bound to Human Leucocyte Antigen (HLA) class I and II complexes. Their immunogenicity has been confirmed through CD4<jats:sup>+<\/jats:sup> and CD8<jats:sup>+<\/jats:sup> T cell-mediated responses in T1D patients. Spliced peptides theoretically have a large sequence variability. This might increase the frequency of viral-human <jats:italic>zwitter<\/jats:italic> peptides<jats:italic>, i.e.<\/jats:italic> peptides that share a complete sequence homology irrespective of whether they originate from human or viral antigens, thereby impinging upon the discrimination between self and non-self antigens by T cells. This might increase the risk of autoimmune responses triggered by viral infections. Since enteroviruses and other viral infections have historically been associated with T1D, we investigated whether <jats:italic>cis<\/jats:italic>-spliced peptides derived from selected viruses might be able to trigger CD8<jats:sup>+<\/jats:sup> T cell-mediated autoimmunity. We computed <jats:italic>in silico<\/jats:italic> viral-human non-spliced and <jats:italic>cis<\/jats:italic>-spliced <jats:italic>zwitter<\/jats:italic> epitope candidates, and prioritized peptide candidates based on: (i) their binding affinity to HLA class I complexes, (ii) human pancreatic \u03b2 cell and medullary thymic epithelial cell (mTEC) antigens\u2019 mRNA expression, (iii) antigen association with T1D, and (iv) potential hotspot regions in those antigens. Neglecting potential T cell receptor (TCR) degeneracy, no viral-human <jats:italic>zwitter<\/jats:italic> non-spliced peptide was found to be an optimal candidate to trigger a virus-induced CD8<jats:sup>+<\/jats:sup> T cell response against human pancreatic \u03b2 cells. Conversely, we identified some <jats:italic>zwitter<\/jats:italic> peptide candidates, which may be produced by proteasome-catalyzed peptide splicing, and might increase the likelihood of pancreatic \u03b2 cells recognition by virus-specific CD8<jats:sup>+<\/jats:sup> T cell clones, therefore promoting \u03b2 cell destruction in the context of viral infections.<\/jats:p>","DOI":"10.3389\/fimmu.2021.656451","type":"journal-article","created":{"date-parts":[[2021,4,16]],"date-time":"2021-04-16T02:56:25Z","timestamp":1618541785000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":15,"title":["Potential Mimicry of Viral and Pancreatic \u03b2 Cell Antigens Through Non-Spliced and cis-Spliced Zwitter Epitope Candidates in Type 1 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