{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T20:06:01Z","timestamp":1789070761097,"version":"build-2803163510"},"reference-count":56,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,9,16]],"date-time":"2022-09-16T00:00:00Z","timestamp":1663286400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R56-AI-15348 , R21-AI-149655 , T32-AI-074491"],"award-info":[{"award-number":["R56-AI-15348 , R21-AI-149655 , T32-AI-074491"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["P30-DK-116073"],"award-info":[{"award-number":["P30-DK-116073"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>The calcitonin gene-related peptide (CGRP) is a 37-amino acid neuropeptide with critical roles in the development of peripheral sensitization and pain. One of the CGRP family peptides, islet amyloid polypeptide (IAPP), is an important autoantigen in type 1 diabetes. Due to the high structural and chemical similarity between CGRP and IAPP, we expected that the CGRP peptide could be recognized by IAPP-specific CD4 T cells. However, there was no cross-reactivity between the CGRP peptide and the diabetogenic IAPP-reactive T cells. A set of CGRP-specific CD4 T cells was isolated from non-obese diabetic (NOD) mice. The T-cell receptor (TCR) variable regions of both \u03b1 and \u03b2 chains were highly skewed towards TRAV13 and TRBV13, respectively. The clonal expansion of T cells suggested that the presence of activated T cells responded to CGRP stimulation. None of the CGRP-specific CD4 T cells were able to be activated by the IAPP peptide. This established that CGRP-reactive CD4 T cells are a unique type of autoantigen-specific T cells in NOD mice. Using IA<jats:sup>g7<\/jats:sup>-CGRP tetramers, we found that CGRP-specific T cells were present in the pancreas of both prediabetic and diabetic NOD mice. The percentages of CGRP-reactive T cells in the pancreas of NOD mice were correlated to the diabetic progression. We showed that the human CGRP peptide presented by IA<jats:sup>g7<\/jats:sup>elicited strong CGRP-specific T-cell responses. These findings suggested that CGRP is a potential autoantigen for CD4 T cells in NOD mice and probably in humans. The CGRP-specific CD4 T cells could be a unique marker for type 1 diabetes. Given the ubiquity of CGRP in nervous systems, it could potentially play an important role in diabetic neuropathy.<\/jats:p>","DOI":"10.3389\/fimmu.2022.951281","type":"journal-article","created":{"date-parts":[[2022,9,16]],"date-time":"2022-09-16T10:42:03Z","timestamp":1663324923000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Calcitonin gene-related peptide is a potential autoantigen for CD4 T cells in type 1 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