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It has become increasingly clear that insulin, and its precursors preproinsulin (PPI) and proinsulin (PI), can play another role\u2014not as a hormone but as an autoantigen in T1D. Here we review the role played by the products of the <jats:italic>INS<\/jats:italic> gene as autoantigens in people with T1D. From many elegant animal studies, it is clear that T\u2010cell responses to insulin, PPI and PI are essential for T1D to develop. Here we review the evidence that autoimmune responses to insulin and PPI arise in people with T1D and discuss the recently described neoepitopes derived from the products of the insulin gene. Finally, we look forward to new approaches to deliver epitopes derived from PPI, PI and insulin that may allow immune tolerance to pancreatic beta cells to be restored in people with, or at risk of, T1D.<\/jats:p>","DOI":"10.1111\/imcb.12442","type":"journal-article","created":{"date-parts":[[2021,2,3]],"date-time":"2021-02-03T04:31:00Z","timestamp":1612326660000},"page":"448-460","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Insulin\u2019s other life: an autoantigen in type 1 diabetes"],"prefix":"10.1111","volume":"99","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3497-3559","authenticated-orcid":false,"given":"Stuart I","family":"Mannering","sequence":"first","affiliation":[{"name":"Immunology and Diabetes Unit St. Vincent\u2019s Institute of Medical Research Fitzroy VIC Australia"},{"name":"Department of Medicine St. Vincent\u2019s Hospital, University of Melbourne Fitzroy VIC 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