{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T03:01:10Z","timestamp":1793674870599,"version":"4.5.1"},"reference-count":111,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2025,11,28]],"date-time":"2025-11-28T00:00:00Z","timestamp":1764288000000},"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":["25-25-00373"],"award-info":[{"award-number":["25-25-00373"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Type 1 diabetes mellitus (T1DM) is an autoimmune disease caused by the destruction of insulin-producing pancreatic \u03b2-cells by autoreactive T cells. Current treatments, including insulin replacement therapy and various immunotherapies, often modulate but fail to permanently halt the underlying autoimmune process or restore \u03b2-cell function. In this review, we examine T cell receptor (TCR)-based treatment strategies for T1DM. We focus on two main approaches: selective elimination of pathogenic autoreactive T cell clones and induction of immune tolerance using TCR-modified regulatory T cells (TCR-Tregs). We describe key islet autoantigens, including post-translationally modified neoantigens such as fusion insulin peptides, which are crucial for identifying pathogenic TCRs. Next, we will review methodologies for TCR detection and TCR-Treg generation, highlighting their mechanisms of action and impact on various immune cells, including dendritic cells, B cells, and macrophages. We will also examine the potential of CD8+T cell regulatory cells (CD8+Tregs). Finally, we will discuss the future of TCR-based therapy, emphasizing the need to optimize TCR affinity, ensure Tregs\u2019 stability, and develop combination therapies. TCR-based therapy represents a revolutionary approach to restoring immune tolerance in T1DM, providing high specificity and reducing the risk of systemic immuno-suppression compared to traditional treatments.<\/jats:p>","DOI":"10.3390\/ijms262311563","type":"journal-article","created":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T08:13:49Z","timestamp":1764576829000},"page":"11563","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["TCR-Based Antigen-Specific Therapy for Type 1 Diabetes Mellitus: From Editing Autoreactive Clones to Tolerance Induction"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6261-7557","authenticated-orcid":false,"given":"Marina","family":"Fisher","sequence":"first","affiliation":[{"name":"Laboratory of Molecular Immunology, Federal State Budgetary Scientific Institution Research Institute of Fundamental and Clinical Immunology, 630099 Novosibirsk, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Philippova","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Immunology, Federal State Budgetary Scientific Institution Research Institute of Fundamental and Clinical Immunology, 630099 Novosibirsk, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vasily","family":"Kurilin","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Immunology, Federal State Budgetary Scientific Institution Research Institute of Fundamental and Clinical Immunology, 630099 Novosibirsk, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7366-7768","authenticated-orcid":false,"given":"Sergey","family":"Sennikov","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Immunology, Federal State Budgetary Scientific Institution Research Institute of Fundamental and Clinical Immunology, 630099 Novosibirsk, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"112277","DOI":"10.1016\/j.diabres.2025.112277","article-title":"Global Type 1 Diabetes Prevalence, Incidence, and Mortality Estimates 2025: Results from the International Diabetes Federation Atlas, 11th Edition, and the T1D Index Version 3.0","volume":"225","author":"Ogle","year":"2025","journal-title":"Diabetes Res. 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