{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T03:27:35Z","timestamp":1772162855907,"version":"3.50.1"},"reference-count":47,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"790","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Transl. Med."],"published-print":{"date-parts":[[2025,3,19]]},"abstract":"<jats:p>\n                    Type 1 diabetes (T1D) is an autoimmune disease where T cells mediate the destruction of the insulin-producing \u03b2 cells found within the islets of Langerhans in the pancreas. Autoantibodies to \u03b2 cell antigens are the only tests available to detect \u03b2 cell autoimmunity. T cell responses to \u03b2 cell antigens, which are known to cause T1D, can only be measured in research settings because of the complexity of assays and the large blood volumes required. Here, we describe the \u03b2 cell antigen\u2013specific T cell assay (BASTA). BASTA is a simple whole-blood assay that can detect human CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cell responses to \u03b2 cell antigens by measuring antigen-stimulated interleukin-2 (IL-2) production. BASTA is both more sensitive and specific than the CFSE (carboxyfluorescein diacetate succinimidyl ester)\u2013based proliferation assay. We used BASTA to identify the regions of preproinsulin that stimulated T cell responses specifically in blood from people with T1D. BASTA can be done with as little as 2 to 3\u00a0milliliters of blood. We found that effector memory CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells are the primary producers of IL-2 in response to preproinsulin peptides. We then evaluated responses to individual and pooled preproinsulin peptides in a cross-sectional study of pediatric patients: without T1D, without T1D but with a first-degree relative with T1D, or diagnosed with T1D. In contrast with other preproinsulin peptides, full-length C-peptide (PI\n                    <jats:sub>33\u201363<\/jats:sub>\n                    ) showed high specificity for T1D [area under the curve (AUC)\u00a0=\u00a00.86)]. We suggest that BASTA will be a useful tool for monitoring changes in \u03b2 cell\u2013specific CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cell responses both in research and clinical settings.\n                  <\/jats:p>","DOI":"10.1126\/scitranslmed.adt2124","type":"journal-article","created":{"date-parts":[[2025,3,19]],"date-time":"2025-03-19T13:58:39Z","timestamp":1742392719000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":2,"title":["BASTA, a simple whole-blood assay for measuring \u03b2 cell antigen\u2013specific CD4\n                    <sup>+<\/sup>\n                    T cell responses in type 1 diabetes"],"prefix":"10.1126","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-7866-0905","authenticated-orcid":true,"given":"Matthew","family":"Lacorcia","sequence":"first","affiliation":[{"name":"Immunology and Diabetes Unit, St. Vincent\u2019s Institute of Medical Research, Fitzroy, Victoria 3065, Australia."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6469-3377","authenticated-orcid":true,"given":"Pushpak","family":"Bhattacharjee","sequence":"additional","affiliation":[{"name":"Immunology and Diabetes Unit, St. Vincent\u2019s Institute of Medical Research, Fitzroy, Victoria 3065, Australia."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-6188-1431","authenticated-orcid":true,"given":"Abby","family":"Foster","sequence":"additional","affiliation":[{"name":"Immunology and Diabetes Unit, St. Vincent\u2019s Institute of Medical Research, Fitzroy, Victoria 3065, Australia."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4923-0678","authenticated-orcid":true,"given":"Melinda Y.","family":"Hardy","sequence":"additional","affiliation":[{"name":"Immunology Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia."},{"name":"Department of Medical Biology, University of Melbourne, Parkville, Victoria 3010, Australia."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7687-9654","authenticated-orcid":true,"given":"Jason A.","family":"Tye-Din","sequence":"additional","affiliation":[{"name":"Immunology Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia."},{"name":"Department of Medical Biology, University of Melbourne, Parkville, Victoria 3010, Australia."},{"name":"Department of Gastroenterology, Royal Melbourne Hospital, Parkville, Victoria 3050, Australia."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3800-5152","authenticated-orcid":true,"given":"John A.","family":"Karas","sequence":"additional","affiliation":[{"name":"School of Chemistry, University of Melbourne, Parkville, Victoria 3010, Australia."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5197-3529","authenticated-orcid":true,"given":"John M.","family":"Wentworth","sequence":"additional","affiliation":[{"name":"Immunology and Diabetes Unit, St. Vincent\u2019s Institute of Medical Research, Fitzroy, Victoria 3065, Australia."},{"name":"Department of Diabetes and Endocrinology, Royal Melbourne Hospital, Parkville, Victoria 3050, Australia."},{"name":"Department of Medicine, Royal Melbourne Hospital, Parkville, Victoria 3050, Australia."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fergus J.","family":"Cameron","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Diabetes, Royal Children\u2019s Hospital, Parkville, Victoria 3052, Australia."},{"name":"Murdoch Children\u2019s Research Institute, Parkville, Victoria 3052, Australia."},{"name":"Department of Paediatrics, University of Melbourne, Parkville, Victoria 3010, Australia."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3497-3559","authenticated-orcid":true,"given":"Stuart I.","family":"Mannering","sequence":"additional","affiliation":[{"name":"Immunology and Diabetes Unit, St. Vincent\u2019s Institute of Medical Research, Fitzroy, Victoria 3065, Australia."},{"name":"Department of Medicine, University of Melbourne, St. Vincent\u2019s Hospital, Fitzroy, Victoria 3065, Australia."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1111\/cei.12699"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(13)60591-7"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2015.07.014"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2013.6285"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.2337\/db19-0119"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1007\/s13340-019-00414-9"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.2337\/dc15-1419"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-017-4284-5"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa010465"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1902226"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2249.2010.04237.x"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.2337\/db14-0858"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1809208115"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.2337\/dbi19-0022"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1206874"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1183909"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jim.2003.09.004"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-8411(03)00111-2"},{"key":"e_1_3_2_20_2","first-page":"1167","article-title":"Visualizing 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