{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T10:22:41Z","timestamp":1771928561477,"version":"3.50.1"},"reference-count":43,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T00:00:00Z","timestamp":1770163200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Pediatric myocarditis is an inflammatory disease of the heart with heterogeneous clinical presentations and poorly understood immune mechanisms. T cell receptor (TCR) repertoire profiling provides insights into disease-associated adaptive immune responses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We performed high-throughput sequencing of TCR \u03b2 chain CDR3 repertoires from 28 peripheral blood samples of pediatric myocarditis patients (Myo) and nine age-matched healthy controls (NC). Clonal diversity, V and J gene usage, CDR3 length distribution, clonotype sharing, and antigen-specific annotations were systematically analyzed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The Myo group exhibited significantly reduced clonal diversity as measured by D50 and Chao1 indices, accompanied by expansion of large clones and reduced representation of small clones. Distinct biases in V and J gene usage were observed, with increased TRBV14, TRBV28, TRBJ1-1, TRBJ1-2, TRBJ1-5, TRBJ1-6, and TRBJ2-2, and decreased TRBV9, TRBJ2-4, TRBJ2-5, and TRBJ2-7. CDR3 length distribution showed an enrichment of longer sequences in myocarditis patients, alongside altered nucleotide insertions\/deletions and amino acid usage. Clonotype sharing was markedly higher in the Myo group, and 16,460 public clonotypes were detected in \u226510 patients. Database annotation revealed an enrichment of matches to pathogen-associated TCR records, predominantly associated to Mycobacterium tuberculosis, influenza, cytomegalovirus, and Epstein\u2013Barr virus. Seventeen high-frequency clonotypes were highlighted as candidate myocarditis-related TCR signatures based on database matches.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our study demonstrates distinct repertoire remodeling in pediatric myocarditis, characterized by reduced diversity, skewed V\/J gene usage, biased CDR3 composition, and enriched public clonotypes. These findings provide novel insights into disease-related adaptive immune responses and may inform biomarker discovery for diagnosis and therapeutic strategies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1711681","type":"journal-article","created":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T06:47:23Z","timestamp":1770187643000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["TCR \u03b2 CDR3 repertoire remodeling in pediatric myocarditis reveals clonal expansion and disease-associated public clonotypes"],"prefix":"10.3389","volume":"17","author":[{"given":"Xixiong","family":"Lin","sequence":"first","affiliation":[{"name":"Department of Cardiology, Kunming Children\u2019s Hospital","place":["Kunming, Yunnan, China"]},{"name":"Department of Immunology, Center of Immunomolecular Engineering, Zunyi Medical University","place":["Zunyi, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xing","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Kunming Children\u2019s Hospital","place":["Kunming, Yunnan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liping","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Kunming Children\u2019s Hospital","place":["Kunming, Yunnan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Linhu","family":"Hui","sequence":"additional","affiliation":[{"name":"Department of Immunology, Center of Immunomolecular Engineering, Zunyi Medical University","place":["Zunyi, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhongjian","family":"Su","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Kunming Children\u2019s Hospital","place":["Kunming, Yunnan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xingzhu","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Kunming Children\u2019s Hospital","place":["Kunming, Yunnan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bin","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Kunming Children\u2019s Hospital","place":["Kunming, Yunnan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Immunology, Center of Immunomolecular Engineering, Zunyi Medical University","place":["Zunyi, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanfei","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Kunming Children\u2019s Hospital","place":["Kunming, Yunnan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,2,4]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcmg.2022.04.007","article-title":"Myocarditis in children: chasing a gold standard","volume":"15","author":"Grosse-Wortmann","year":"2022","journal-title":"JACC Cardiovasc Imaging"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pcad.2009.11.006","article-title":"Myocarditis","volume":"52","author":"Blauwet","year":"2010","journal-title":"Prog Cardiovasc Dis"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1007\/s11427-022-2273-3","article-title":"Immunopathogenesis and immunomodulatory therapy for myocarditis","volume":"66","author":"He","year":"2023","journal-title":"Sci China Life Sci"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1093\/jleuko\/qiad143","article-title":"Role of immune cells in the pathogenesis of myocarditis","volume":"115","author":"Liu","year":"2024","journal-title":"J Leukoc Biol"},{"key":"B5","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1002\/rmv.2131","article-title":"An overview of the immune mechanisms of viral myocarditis","volume":"30","author":"Lasrado","year":"2020","journal-title":"Rev Med Virol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2023.3371","article-title":"Diagnosis and treatment of acute myocarditis: A review","volume":"329","author":"Ammirati","year":"2023","journal-title":"JAMA"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcm.2020.05.008","article-title":"Update on acute myocarditis","volume":"31","author":"Ammirati","year":"2021","journal-title":"Trends Cardiovasc Med"},{"key":"B8","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1186\/s12967-025-06394-6","article-title":"Cxcl12\/Cxcr4 axis mediates Cd8 (+) T cell overactivation in the progression of viral myocarditis","volume":"23","author":"Zhang","year":"2025","journal-title":"J Transl Med"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.121.056730","article-title":"Identification of pathogenic immune cell subsets associated with checkpoint inhibitor-induced myocarditis","volume":"146","author":"Zhu","year":"2022","journal-title":"Circulation"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1111\/tri.13475","article-title":"T-cell receptor and B-cell receptor repertoire profiling in adaptive immunity","volume":"32","author":"Minervina","year":"2019","journal-title":"Transpl Int"},{"key":"B11","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1016\/s0198-8859(02)00798-x","article-title":"Expansion of specific alphabeta+ T-cell subsets in the myocardium of patients with myocarditis and idiopathic dilated cardiomyopathy associated with Coxsackievirus B infection","volume":"64","author":"Luppi","year":"2003","journal-title":"Hum Immunol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2008.06.002","article-title":"Inhibition of experimental autoimmune myocarditis: peripheral deletion of Tcr Vbeta 8.1, 8.2+ Cd4+ T cells in Tlr-4 deficient mice","volume":"31","author":"Gonnella","year":"2008","journal-title":"J Autoimmun"},{"key":"B13","doi-asserted-by":"publisher","first-page":"394","DOI":"10.1038\/s41435-025-00343-5","article-title":"Peripheral immune imbalance in pediatric fulminant myocarditis revealed by single-cell sequencing and plasma proteomics","volume":"26","author":"Liu","year":"2025","journal-title":"Genes Immun"},{"key":"B14","doi-asserted-by":"publisher","first-page":"234","DOI":"10.3390\/cells13030234","article-title":"Investigation into cardiac myhc-alpha 334-352-specific Tcr transgenic mice reveals a role for cytotoxic Cd4 T cells in the development of cardiac autoimmunity","volume":"13","author":"Sur","year":"2024","journal-title":"Cells"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1002\/eji.202048724","article-title":"Immune response in children with Covid-19 is characterized by lower levels of T-cell activation than infected adults","volume":"50","author":"Moratto","year":"2020","journal-title":"Eur J Immunol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.14336\/AD.2023.0509-1","article-title":"A new immunological index for the elderly: high proportion of multiple Tcr T cells based on Scrna-Seq","volume":"15","author":"Jun","year":"2024","journal-title":"Aging Dis"},{"key":"B17","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1007\/978-1-0716-0904-0_1","article-title":"T cell receptor repertoire sequencing","volume":"2204","author":"Lin","year":"2020","journal-title":"Methods Mol Biol"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.3364","article-title":"Mixcr: software for comprehensive adaptive immunity profiling","volume":"12","author":"Bolotin","year":"2015","journal-title":"Nat Methods"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gki010","article-title":"Imgt\/gene-Db: A comprehensive database for human and mouse immunoglobulin and T cell receptor genes","volume":"33","author":"Giudicelli","year":"2005","journal-title":"Nucleic Acids Res"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1004503","article-title":"Vdjtools: unifying post-analysis of T cell receptor repertoires","volume":"11","author":"Shugay","year":"2015","journal-title":"PloS Comput Biol"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btx286","article-title":"Mcpas-Tcr: A manually curated catalogue of pathology-associated T cell receptor sequences","volume":"33","author":"Tickotsky","year":"2017","journal-title":"Bioinformatics"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkx760","article-title":"Vdjdb: A curated database of T-cell receptor sequences with known antigen specificity","volume":"46","author":"Shugay","year":"2018","journal-title":"Nucleic Acids Res"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(11)60648-X","article-title":"Myocarditis","volume":"379","author":"Sagar","year":"2012","journal-title":"Lancet"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2008.09.021","article-title":"Structural features of T cell receptor variable regions that enhance domain stability and enable expression as single-chain valphavbeta fragments","volume":"46","author":"Richman","year":"2009","journal-title":"Mol Immunol"},{"key":"B25","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1146\/annurev-genet-110410-132552","article-title":"V(D)J recombination: mechanisms of initiation","volume":"45","author":"Schatz","year":"2011","journal-title":"Annu Rev Genet"},{"key":"B26","doi-asserted-by":"publisher","first-page":"825","DOI":"10.3390\/biom13050825","article-title":"Analysis of cdr3 sequences from T-cell receptor beta in acute respiratory distress syndrome","volume":"13","author":"Hey","year":"2023","journal-title":"Biomolecules"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1101\/gr.092924.109","article-title":"Profiling the T-cell receptor beta-chain repertoire by massively parallel sequencing","volume":"19","author":"Freeman","year":"2009","journal-title":"Genome Res"},{"key":"B28","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1186\/s12967-019-1788-4","article-title":"Peripheral T cell receptor beta immune repertoire is promptly reconstituted after acute myocardial infarction","volume":"17","author":"Li","year":"2019","journal-title":"J Transl Med"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-024-08105-5","article-title":"Immune responses in checkpoint myocarditis across heart, blood and tumour","volume":"636","author":"Blum","year":"2024","journal-title":"Nature"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.164.4.2248","article-title":"Successful Tcr-based immunotherapy for autoimmune myocarditis with DNA vaccines after rapid identification of pathogenic Tcr","volume":"164","author":"Matsumoto","year":"2000","journal-title":"J Immunol"},{"key":"B31","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1016\/j.molimm.2020.01.024","article-title":"High-throughput sequencing reveals the diversity of Tcr beta chain Cdr3 repertoire in patients with severe acne","volume":"120","author":"Shao","year":"2020","journal-title":"Mol Immunol"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1038\/cmi.2014.134","article-title":"Alphabeta T cell receptors as predictors of health and disease","volume":"12","author":"Attaf","year":"2015","journal-title":"Cell Mol Immunol"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-021-00927-z","article-title":"Hallmarks of T cell aging","volume":"22","author":"Mittelbrunn","year":"2021","journal-title":"Nat Immunol"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1007\/s00281-021-00840-5","article-title":"Dynamics of thymus function and T cell receptor repertoire breadth in health and disease","volume":"43","author":"Granadier","year":"2021","journal-title":"Semin Immunopathol"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0904193","article-title":"Loss of naive T cells and repertoire constriction predict poor response to vaccination in old primates","volume":"184","author":"Cicin-Sain","year":"2010","journal-title":"J Immunol"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1093\/eurjhf\/hfr014","article-title":"Expression of functional T-cell markers and T-cell receptor Vbeta repertoire in endomyocardial biopsies from patients presenting with acute myocarditis and dilated cardiomyopathy","volume":"13","author":"Noutsias","year":"2011","journal-title":"Eur J Heart Fail"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.743448","article-title":"Longitudinal high-throughput sequencing of the T-cell receptor repertoire reveals dynamic change and prognostic significance of peripheral blood Tcr diversity in metastatic colorectal cancer during chemotherapy","volume":"12","author":"Chen","year":"2021","journal-title":"Front Immunol"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/dxh046","article-title":"Development of Tcrb Cdr3 length repertoire of human T lymphocytes","volume":"16","author":"Nishio","year":"2004","journal-title":"Int Immunol"},{"key":"B39","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1186\/s40959-024-00230-4","article-title":"Reconstitution of peripheral blood T cell receptor beta immune repertoire in immune checkpoint inhibitors associated myocarditis","volume":"10","author":"Yan","year":"2024","journal-title":"Cardiooncology"},{"key":"B40","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/s0165-5728(00)00346-5","article-title":"Characterization of T cell receptor (Tcr) of organ-specific autoimmune disease-inducing T cells and Tcr-based immunotherapy with DNA vaccines","volume":"110","author":"Matsumoto","year":"2000","journal-title":"J Neuroimmunol"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.122.059970","article-title":"Risk of myocarditis after sequential doses of Covid-19 vaccine and Sars-Cov-2 infection by age and sex","volume":"146","author":"Patone","year":"2022","journal-title":"Circulation"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2023.104810","article-title":"Understanding yellow fever-associated myocardial injury: an autopsy study","volume":"96","author":"Giugni","year":"2023","journal-title":"EBioMedicine"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/cit403","article-title":"Evaluation of cardiac involvement during dengue viral infection","volume":"57","author":"Miranda","year":"2013","journal-title":"Clin Infect Dis"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1711681\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T09:31:23Z","timestamp":1771925483000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1711681\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,4]]},"references-count":43,"alternative-id":["10.3389\/fimmu.2026.1711681"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1711681","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,4]]},"article-number":"1711681"}}