{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T07:18:27Z","timestamp":1791875907277,"version":"4.3.4"},"reference-count":85,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2023,9,25]],"date-time":"2023-09-25T00:00:00Z","timestamp":1695600000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institutes of Health","award":["5R21AI142281"],"award-info":[{"award-number":["5R21AI142281"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Myocarditis is a predominant cause of congestive heart failure and sudden death in children and young adolescents that can lead to dilated cardiomyopathy. Lymphocytic myocarditis mediated by T cells can result from the recognition of cardiac antigens that may involve CD4 or CD8 T cells or both. In this report, we describe the generation of T cell receptor (TCR) transgenic mice on a C57BL\/6 genetic background specific to cardiac myosin heavy chain (Myhc)-\u03b1 334\u2013352 and make the following observations: First, we verified that Myhc-\u03b1 334\u2013352 was immunogenic in wild-type C57BL\/6 mice and induced antigen-specific CD4 T cell responses despite being a poor binder of IAb; however, the immunized animals developed only mild myocarditis. Second, TCRs specific to Myhc-\u03b1 334\u2013352 in transgenic mice were expressed in both CD4 and CD8 T cells, suggesting that the expression of epitope-specific TCR is common to both cell types. Third, although T cells from na\u00efve transgenic mice did not respond to Myhc-\u03b1 334\u2013352, both CD4 and CD8 T cells from animals immunized with Myhc-\u03b1 334\u2013352 responded to the peptide, indicating that antigen priming is necessary to break tolerance. Fourth, although the transgenic T cells could produce significant amounts of interferon-\u03b3 and interleukin-17, the immunized animals developed only mild disease, indicating that other soluble factors might be necessary for developing severe myocarditis. Alternatively, the C57BL\/6 genetic background might be a major contributing factor for resistance to the development of myocarditis. Taken together, our model permits the determination of the roles of both CD4 and CD8 T cells to understand the disease-resistance mechanisms of myocarditis in a single transgenic system antigen-specifically.<\/jats:p>","DOI":"10.3390\/cells12192346","type":"journal-article","created":{"date-parts":[[2023,9,25]],"date-time":"2023-09-25T03:56:49Z","timestamp":1695614209000},"page":"2346","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Transgenic Mice Expressing Functional TCRs Specific to Cardiac Myhc-\u03b1 334\u2013352 on Both CD4 and CD8 T Cells Are Resistant to the Development of Myocarditis on C57BL\/6 Genetic Background"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0878-4930","authenticated-orcid":false,"given":"Meghna","family":"Sur","sequence":"first","affiliation":[{"name":"School of Veterinary Medicine and Biomedical Sciences, University of Nebraska-Lincoln, Lincoln, NE 68583, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0923-4869","authenticated-orcid":false,"given":"Mahima T.","family":"Rasquinha","sequence":"additional","affiliation":[{"name":"School of Veterinary Medicine and Biomedical Sciences, University of Nebraska-Lincoln, Lincoln, NE 68583, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7021-7884","authenticated-orcid":false,"given":"Rajkumar","family":"Arumugam","sequence":"additional","affiliation":[{"name":"School of Veterinary Medicine and Biomedical Sciences, University of Nebraska-Lincoln, Lincoln, NE 68583, USA"},{"name":"Bristol Myers Squibb, Summit, NJ 07901, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chandirasegaran","family":"Massilamany","sequence":"additional","affiliation":[{"name":"School of Veterinary Medicine and Biomedical Sciences, University of Nebraska-Lincoln, Lincoln, NE 68583, USA"},{"name":"CRISPR Therapeutics, Boston, MA 02127, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arunkumar","family":"Gangaplara","sequence":"additional","affiliation":[{"name":"School of Veterinary Medicine and Biomedical Sciences, University of Nebraska-Lincoln, Lincoln, NE 68583, USA"},{"name":"Miltenyi Biotec, Gaithersburg, MD 20878, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiruthiga","family":"Mone","sequence":"additional","affiliation":[{"name":"School of Veterinary Medicine and Biomedical Sciences, University of Nebraska-Lincoln, Lincoln, NE 68583, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6762-2654","authenticated-orcid":false,"given":"Ninaad","family":"Lasrado","sequence":"additional","affiliation":[{"name":"School of Veterinary Medicine and Biomedical Sciences, University of Nebraska-Lincoln, Lincoln, NE 68583, USA"},{"name":"Center for Virology and Vaccine Research, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bharathi","family":"Yalaka","sequence":"additional","affiliation":[{"name":"School of Veterinary Medicine and Biomedical Sciences, University of Nebraska-Lincoln, Lincoln, NE 68583, USA"},{"name":"Bristol Myers Squibb, Summit, NJ 07901, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aakash","family":"Doiphode","sequence":"additional","affiliation":[{"name":"School of Veterinary Medicine and Biomedical Sciences, University of Nebraska-Lincoln, Lincoln, NE 68583, USA"},{"name":"Department of Animal Genetics and Breeding, Krantisinh Nana Patil College of Veterinary Science, Shirwal 412801, Maharashtra, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Channabasavaiah","family":"Gurumurthy","sequence":"additional","affiliation":[{"name":"Department of Genetics, Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, NE 68198, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5166-2296","authenticated-orcid":false,"given":"David","family":"Steffen","sequence":"additional","affiliation":[{"name":"School of Veterinary Medicine and Biomedical Sciences, University of Nebraska-Lincoln, Lincoln, NE 68583, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4082-9254","authenticated-orcid":false,"given":"Jay","family":"Reddy","sequence":"additional","affiliation":[{"name":"School of Veterinary Medicine and Biomedical Sciences, University of Nebraska-Lincoln, Lincoln, NE 68583, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,9,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.1161\/CIRCULATIONAHA.108.804617","article-title":"Sudden deaths in young competitive athletes: Analysis of 1866 deaths in the United States, 1980-2006","volume":"119","author":"Maron","year":"2009","journal-title":"Circulation"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1161\/CIRCRESAHA.117.310221","article-title":"Inflammatory Cardiomyopathic Syndromes","volume":"121","author":"Trachtenberg","year":"2017","journal-title":"Circ. Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1097\/00045415-199905000-00009","article-title":"Cardiovascular causes of sudden death in young individuals including athletes","volume":"7","author":"Basso","year":"1999","journal-title":"Cardiol. Rev."},{"key":"ref_4","first-page":"197","article-title":"A Review of Sudden Cardiac Death in Young Athletes and Strategies for Preparticipation Cardiovascular Screening","volume":"36","author":"Koester","year":"2001","journal-title":"J. Athl. Train"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1111\/j.1600-0838.1995.tb00045.x","article-title":"Sudden death and physical activity in athletes and nonathletes","volume":"5","year":"1995","journal-title":"Scand. J. Med. Sci. Sports"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2636","DOI":"10.1093\/eurheartj\/eht210","article-title":"Current state of knowledge on aetiology, diagnosis, management, and therapy of myocarditis: A position statement of the European Society of Cardiology Working Group on Myocardial and Pericardial Diseases","volume":"34","author":"Caforio","year":"2013","journal-title":"Eur. Heart J."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Rroku, A., Kottwitz, J., and Heidecker, B. (2020). Update on myocarditis\u2014What we know so far and where we may be heading. Eur. Heart J. Acute Cardiovasc. Care.","DOI":"10.1177\/2048872620910109"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1161\/01.CIR.0000155616.07901.35","article-title":"High prevalence of viral genomes and multiple viral infections in the myocardium of adults with \u201cidiopathic\u201d left ventricular dysfunction","volume":"111","author":"Kuhl","year":"2005","journal-title":"Circulation"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Krejci, J., Mlejnek, D., Sochorova, D., and Nemec, P. (2016). Inflammatory Cardiomyopathy: A Current View on the Pathophysiology, Diagnosis, and Treatment. Biomed. Res. Int., 2016.","DOI":"10.1155\/2016\/4087632"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1245","DOI":"10.5114\/aoms.2018.79002","article-title":"Viral genome changes and the impact of viral genome persistence in myocardium of patients with inflammatory cardiomyopathy","volume":"14","author":"Mlejnek","year":"2018","journal-title":"Arch. Med. Sci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1007\/s001470100339","article-title":"Histopathologic findings in explanted heart tissue from patients with end-stage idiopathic dilated cardiomyopathy","volume":"14","author":"Ruiter","year":"2001","journal-title":"Transpl. Int."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1867","DOI":"10.1001\/jama.296.15.1867","article-title":"Incidence, causes, and outcomes of dilated cardiomyopathy in children","volume":"296","author":"Towbin","year":"2006","journal-title":"JAMA"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1056","DOI":"10.1016\/j.healun.2019.08.004","article-title":"The International Thoracic Organ Transplant Registry of the International Society for Heart and Lung Transplantation: Thirty-sixth adult heart transplantation report\u20142019; focus theme: Donor and recipient size match","volume":"38","author":"Khush","year":"2019","journal-title":"J. Heart Lung Transplant."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1007\/s00428-019-02615-8","article-title":"The spectrum of myocarditis: From pathology to the clinics","volume":"475","author":"Leone","year":"2019","journal-title":"Virchows Arch."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e007405","DOI":"10.1161\/CIRCHEARTFAILURE.120.007405","article-title":"Management of Acute Myocarditis and Chronic Inflammatory Cardiomyopathy: An Expert Consensus Document","volume":"13","author":"Ammirati","year":"2020","journal-title":"Circ. Heart Fail."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1161\/01.RES.64.1.97","article-title":"Autoantibodies against beta-adrenoceptors in human idiopathic dilated cardiomyopathy","volume":"64","author":"Limas","year":"1989","journal-title":"Circ. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1161\/CIRCRESAHA.111.243360","article-title":"Autoantibodies in heart failure and cardiac dysfunction","volume":"110","author":"Kaya","year":"2012","journal-title":"Circ. Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.1016\/S0735-1097(02)02075-2","article-title":"Autoantibodies produced against sarcolemmal Na-K-ATPase: Possible upstream targets of arrhythmias and sudden death in patients with dilated cardiomyopathy","volume":"40","author":"Baba","year":"2002","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/j.ijcard.2006.04.077","article-title":"Autoantibodies to cardiac troponin I in patients with idiopathic dilated and ischemic cardiomyopathy","volume":"117","author":"Shmilovich","year":"2007","journal-title":"Int. J. Cardiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"99","DOI":"10.3109\/08916939409009537","article-title":"Complement-mediated cytotoxic activity of anti-heart antibodies present in the sera of patients with dilated cardiomyopathy","volume":"19","author":"Latif","year":"1994","journal-title":"Autoimmunity"},{"key":"ref_21","first-page":"283","article-title":"Demonstration of organ specific antibodies against heart mitochondria (anti-M7) in sera from patients with some forms of heart diseases","volume":"58","author":"Klein","year":"1984","journal-title":"Clin. Exp. Immunol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"85","DOI":"10.3109\/08916939508993354","article-title":"Dilated cardiomyopathy defines serum autoantibodies against G-protein-coupled cardiovascular receptors","volume":"21","author":"Matsui","year":"1995","journal-title":"Autoimmunity"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"4754","DOI":"10.4049\/jimmunol.153.10.4754","article-title":"Epitope mapping of the branched chain alpha-ketoacid dehydrogenase dihydrolipoyl transacylase (BCKD-E2) protein that reacts with sera from patients with idiopathic dilated cardiomyopathy","volume":"153","author":"Ansari","year":"1994","journal-title":"J. Immunol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1734","DOI":"10.1161\/01.CIR.85.5.1734","article-title":"Identification of alpha- and beta-cardiac myosin heavy chain isoforms as major autoantigens in dilated cardiomyopathy","volume":"85","author":"Caforio","year":"1992","journal-title":"Circulation"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1016\/S0022-2828(85)80029-8","article-title":"Immunological analysis of auto-antibodies against the adenine nucleotide translocator in dilated cardiomyopathy","volume":"17","author":"Schultheiss","year":"1985","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"3914","DOI":"10.1111\/bph.13613","article-title":"T-cell immunity in myocardial inflammation: Pathogenic role and therapeutic manipulation","volume":"174","author":"Stephenson","year":"2017","journal-title":"Br. J. Pharmacol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1007\/978-3-319-57613-8_10","article-title":"Cardiac Autoimmunity: Myocarditis","volume":"1003","author":"Cihakova","year":"2017","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"64","DOI":"10.3389\/fcvm.2019.00064","article-title":"Myocarditis in Humans and in Experimental Animal Models","volume":"6","author":"Blyszczuk","year":"2019","journal-title":"Front. Cardiovasc. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"523","DOI":"10.4049\/jimmunol.1701090","article-title":"Epitope Mapping of SERCA2a Identifies an Antigenic Determinant That Induces Mainly Atrial Myocarditis in A\/J Mice","volume":"200","author":"Krishnan","year":"2018","journal-title":"J. Immunol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1567","DOI":"10.3389\/fimmu.2017.01567","article-title":"beta1-Adrenergic Receptor Contains Multiple IA(k) and IE(k) Binding Epitopes That Induce T Cell Responses with Varying Degrees of Autoimmune Myocarditis in A\/J Mice","volume":"8","author":"Basavalingappa","year":"2017","journal-title":"Front. Immunol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1002\/iid3.177","article-title":"Branched chain alpha-ketoacid dehydrogenase kinase 111-130, a T cell epitope that induces both autoimmune myocarditis and hepatitis in A\/J mice","volume":"5","author":"Krishnan","year":"2017","journal-title":"Immun. Inflamm. Dis."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.clim.2009.04.008","article-title":"Cardiac troponins and autoimmunity: Their role in the pathogenesis of myocarditis and of heart failure","volume":"134","author":"Kaya","year":"2010","journal-title":"Clin. Immunol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.jim.2011.07.004","article-title":"Detection of cardiac myosin heavy chain-alpha-specific CD4 cells by using MHC class II\/IA(k) tetramers in A\/J mice","volume":"372","author":"Massilamany","year":"2011","journal-title":"J. Immunol. Methods"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"3160","DOI":"10.1016\/j.ajpath.2016.08.005","article-title":"Identification of an Epitope from Adenine Nucleotide Translocator 1 That Induces Inflammation in Heart in A\/J Mice","volume":"186","author":"Basavalingappa","year":"2016","journal-title":"Am. J. Pathol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2057","DOI":"10.1172\/JCI118642","article-title":"Identification of cardiac myosin peptides capable of inducing autoimmune myocarditis in BALB\/c mice","volume":"97","author":"Pummerer","year":"1996","journal-title":"J. Clin. Investig."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"892","DOI":"10.4049\/jimmunol.153.2.892","article-title":"Identification of myocarditogenic peptides derived from cardiac myosin capable of inducing experimental allergic myocarditis in the Lewis rat. The utility of a class II binding motif in selecting self-reactive peptides","volume":"153","author":"Wegmann","year":"1994","journal-title":"J. Immunol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.jim.2015.08.007","article-title":"Versatility of using major histocompatibility complex class II dextramers for derivation and characterization of antigen-specific, autoreactive T cell hybridomas","volume":"426","author":"Krishnan","year":"2015","journal-title":"J. Immunol. Methods"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/0022-1759(95)00002-R","article-title":"Cassette vectors directing expression of T cell receptor genes in transgenic mice","volume":"180","author":"Kouskoff","year":"1995","journal-title":"J. Immunol. Methods"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Massilamany, C., Upadhyaya, B., Gangaplara, A., Kuszynski, C., and Reddy, J. (2011). Detection of autoreactive CD4 T cells using major histocompatibility complex class II dextramers. BMC Immunol., 12.","DOI":"10.1186\/1471-2172-12-40"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Massilamany, C., Gangaplara, A., Jia, T., Elowsky, C., Kang, G., Riethoven, J.J., Li, Q., Zhou, Y., and Reddy, J. (2014). Direct staining with major histocompatibility complex class II dextramers permits detection of antigen-specific, autoreactive CD4 T cells in situ. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0087519"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1038\/nm1564","article-title":"Myelin-specific regulatory T cells accumulate in the CNS but fail to control autoimmune inflammation","volume":"13","author":"Korn","year":"2007","journal-title":"Nat. Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"870","DOI":"10.4049\/jimmunol.170.2.870","article-title":"Detection of autoreactive myelin proteolipid protein 139-151-specific T cells by using MHC II (IAs) tetramers","volume":"170","author":"Reddy","year":"2003","journal-title":"J. Immunol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"4175","DOI":"10.4049\/jimmunol.171.8.4175","article-title":"Ex vivo analysis of thymic CD4 T cells in nonobese diabetic mice with tetramers generated from I-A(g7)\/class II-associated invariant chain peptide precursors","volume":"171","author":"Jang","year":"2003","journal-title":"J. Immunol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.jneuroim.2013.08.006","article-title":"Mimicry epitope from Ehrlichia canis for interphotoreceptor retinoid-binding protein 201-216 prevents autoimmune uveoretinitis by acting as altered peptide ligand","volume":"263","author":"Gangaplara","year":"2013","journal-title":"J. Neuroimmunol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1291","DOI":"10.1084\/jem.182.5.1291","article-title":"Myocarditis-inducing epitope of myosin binds constitutively and stably to I-Ak on antigen-presenting cells in the heart","volume":"182","author":"Donermeyer","year":"1995","journal-title":"J. Exp. Med."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/S0002-9440(10)61685-9","article-title":"Experimental autoimmune myocarditis in A\/J mice is an interleukin-4-dependent disease with a Th2 phenotype","volume":"159","author":"Afanasyeva","year":"2001","journal-title":"Am. J. Pathol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2141","DOI":"10.4049\/jimmunol.147.7.2141","article-title":"Myosin-induced acute myocarditis is a T cell-mediated disease","volume":"147","author":"Smith","year":"1991","journal-title":"J. Immunol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1016\/j.ijcard.2015.09.016","article-title":"Localization of CD8 T cell epitope within cardiac myosin heavy chain-alpha334-352 that induces autoimmune myocarditis in A\/J mice","volume":"202","author":"Massilamany","year":"2016","journal-title":"Int. J. Cardiol"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"16663","DOI":"10.1021\/bi991393l","article-title":"Ovalbumin(323-339) peptide binds to the major histocompatibility complex class II I-A(d) protein using two functionally distinct registers","volume":"38","author":"McFarland","year":"1999","journal-title":"Biochemistry"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1111\/imm.12032","article-title":"Combination peptide immunotherapy based on T-cell epitope mapping reduces allergen-specific IgE and eosinophilia in allergic airway inflammation","volume":"138","author":"Mackenzie","year":"2013","journal-title":"Immunology"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1523","DOI":"10.1093\/intimm\/9.10.1523","article-title":"The role of I-Ag7 beta chain in peptide binding and antigen recognition by T cells","volume":"9","author":"Kanagawa","year":"1997","journal-title":"Int. Immunol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.jneuroim.2009.11.006","article-title":"An epitope from Acanthamoeba castellanii that cross-react with proteolipid protein 139-151-reactive T cells induces autoimmune encephalomyelitis in SJL mice","volume":"219","author":"Massilamany","year":"2010","journal-title":"J. Neuroimmunol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1016\/j.cellimm.2011.08.013","article-title":"Identification of novel mimicry epitopes for cardiac myosin heavy chain-alpha that induce autoimmune myocarditis in A\/J mice","volume":"271","author":"Massilamany","year":"2011","journal-title":"Cell Immunol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1524","DOI":"10.1523\/JNEUROSCI.11-06-01524.1991","article-title":"Wocko, a neurological mutant generated in a transgenic mouse pedigree","volume":"11","author":"Crenshaw","year":"1991","journal-title":"J. Neurosci."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1093\/genetics\/136.1.247","article-title":"Insertional mutation on mouse chromosome 18 with vestibular and craniofacial abnormalities","volume":"136","author":"Ting","year":"1994","journal-title":"Genetics"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Silaeva, Y.Y., Kalinina, A.A., Khromykh, L.M., and Kazansky, D.B. (2018). Functional properties of CD8+ T cells under lymphopenic conditions. bioRxiv.","DOI":"10.1101\/353011"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/0165-5728(88)90032-X","article-title":"Characterization of a major encephalitogenic T cell epitope in SJL\/J mice with synthetic oligopeptides of myelin basic protein","volume":"19","author":"Sakai","year":"1988","journal-title":"J. Neuroimmunol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"3630","DOI":"10.4049\/jimmunol.139.11.3630","article-title":"Cardiac myosin induces myocarditis in genetically predisposed mice","volume":"139","author":"Neu","year":"1987","journal-title":"J. Immunol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1084\/jem.20021603","article-title":"Myelin oligodendrocyte glycoprotein-specific T cell receptor transgenic mice develop spontaneous autoimmune optic neuritis","volume":"197","author":"Bettelli","year":"2003","journal-title":"J. Exp. Med."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"3412","DOI":"10.1073\/pnas.97.7.3412","article-title":"Fulminant spontaneous autoimmunity of the central nervous system in mice transgenic for the myelin proteolipid protein-specific T cell receptor","volume":"97","author":"Waldner","year":"2000","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"2084","DOI":"10.4049\/jimmunol.1102186","article-title":"A transgenic model of central nervous system autoimmunity mediated by CD4+ and CD8+ T and B cells","volume":"188","author":"Anderson","year":"2012","journal-title":"J. Immunol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"9131","DOI":"10.1073\/pnas.89.19.9131","article-title":"Expression of myosin-class II major histocompatibility complexes in the normal myocardium occurs before induction of autoimmune myocarditis","volume":"89","author":"Smith","year":"1992","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1038\/nm.2104","article-title":"Development of replication-defective lymphocytic choriomeningitis virus vectors for the induction of potent CD8+ T cell immunity","volume":"16","author":"Flatz","year":"2010","journal-title":"Nat. Med."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1016\/0092-8674(93)90074-Z","article-title":"Transgenic mice that express a myelin basic protein-specific T cell receptor develop spontaneous autoimmunity","volume":"72","author":"Goverman","year":"1993","journal-title":"Cell"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"497","DOI":"10.4049\/jimmunol.159.1.497","article-title":"Triggers of autoimmune disease in a murine TCR-transgenic model for multiple sclerosis","volume":"159","author":"Brabb","year":"1997","journal-title":"J. Immunol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1449","DOI":"10.1084\/jem.20132126","article-title":"Cardiac fibroblasts mediate IL-17A-driven inflammatory dilated cardiomyopathy","volume":"211","author":"Wu","year":"2014","journal-title":"J. Exp. Med."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"4038","DOI":"10.4049\/jimmunol.1301282","article-title":"Fatal eosinophilic myocarditis develops in the absence of IFN-gamma and IL-17A","volume":"191","author":"Barin","year":"2013","journal-title":"J. Immunol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"2163","DOI":"10.1073\/pnas.1416922112","article-title":"IL-4 abrogates T(H)17 cell-mediated inflammation by selective silencing of IL-23 in antigen-presenting cells","volume":"112","author":"Guenova","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1016\/j.recesp.2019.07.013","article-title":"Interleukin-5 levels are decreased in the plasma of coronary artery disease patients and inhibit Th1 and Th17 differentiation in vitro","volume":"73","author":"Ye","year":"2020","journal-title":"Rev. Esp. Cardiol. Engl. Ed."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"2305","DOI":"10.1016\/j.jaci.2020.11.036","article-title":"Mast cell-derived IL-13 downregulates IL-12 production by skin dendritic cells to inhibit the T(H)1 cell response to cutaneous antigen exposure","volume":"147","author":"Das","year":"2021","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1807","DOI":"10.1002\/eji.200838331","article-title":"Interleukin 10 suppresses Th17 cytokines secreted by macrophages and T cells","volume":"38","author":"Gu","year":"2008","journal-title":"Eur. J. Immunol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"2311","DOI":"10.1002\/eji.201142209","article-title":"Cooperation of Th1 and Th17 cells determines transition from autoimmune myocarditis to dilated cardiomyopathy","volume":"42","author":"Nindl","year":"2012","journal-title":"Eur. J. Immunol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"7574","DOI":"10.1073\/pnas.95.13.7574","article-title":"Definition of MHC and T cell receptor contacts in the HLA-DR4restricted immunodominant epitope in type II collagen and characterization of collagen-induced arthritis in HLA-DR4 and human CD4 transgenic mice","volume":"95","author":"Andersson","year":"1998","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"928","DOI":"10.1002\/eji.1830260431","article-title":"Specificity of an HLA-DRB1*0401-restricted T cell response to type II collagen","volume":"26","author":"Fugger","year":"1996","journal-title":"Eur. J. Immunol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.1084\/jem.185.6.1113","article-title":"An HLA-DR1 transgene confers susceptibility to collagen-induced arthritis elicited with human type II collagen","volume":"185","author":"Rosloniec","year":"1997","journal-title":"J. Exp. Med."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1497","DOI":"10.1002\/1529-0131(199907)42:7<1497::AID-ANR25>3.0.CO;2-#","article-title":"T cell responses to a human cartilage autoantigen in the context of rheumatoid arthritis-associated and nonassociated HLA-DR4 alleles","volume":"42","author":"Cope","year":"1999","journal-title":"Arthritis Rheum."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"2597","DOI":"10.1172\/JCI119079","article-title":"Naturally processed T cell epitopes from human glutamic acid decarboxylase identified using mice transgenic for the type 1 diabetes-associated human MHC class II allele, DRB1*0401","volume":"98","author":"Wicker","year":"1996","journal-title":"J. Clin. Investig."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"8082","DOI":"10.1073\/pnas.94.15.8082","article-title":"Identification of immunodominant T cell epitopes of human glutamic acid decarboxylase 65 by using HLA-DR(alpha1*0101,beta1*0401) transgenic mice","volume":"94","author":"Patel","year":"1997","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1084\/jem.181.3.867","article-title":"The T cell response of HLA-DR transgenic mice to human myelin basic protein and other antigens in the presence and absence of human CD4","volume":"181","author":"Altmann","year":"1995","journal-title":"J. Exp. Med."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1093\/eurheartj\/ehv639","article-title":"Role of T-cells in myocardial infarction","volume":"37","author":"Hofmann","year":"2016","journal-title":"Eur. Heart J."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1038\/cmi.2014.74","article-title":"Characterization of CD8(+)CD57(+) T cells in patients with acute myocardial infarction","volume":"12","author":"Youn","year":"2015","journal-title":"Cell Mol. Immunol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1161\/CIRCRESAHA.116.304072","article-title":"Role of lymphocytes in myocardial injury, healing, and remodeling after myocardial infarction","volume":"116","author":"Hofmann","year":"2015","journal-title":"Circ. Res."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1016\/j.molimm.2020.06.017","article-title":"Viral myocarditis involves the generation of autoreactive T cells with multiple antigen specificities that localize in lymphoid and non-lymphoid organs in the mouse model of CVB3 infection","volume":"124","author":"Basavalingappa","year":"2020","journal-title":"Mol. Immunol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1724","DOI":"10.4049\/jimmunol.176.3.1724","article-title":"Experimental African trypanosomiasis: A subset of pathogenic, IFN-gamma-producing, MHC class II-restricted CD4+ T cells mediates early mortality in highly susceptible mice","volume":"176","author":"Shi","year":"2006","journal-title":"J. Immunol."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/12\/19\/2346\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:57:24Z","timestamp":1760129844000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/12\/19\/2346"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9,25]]},"references-count":85,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2023,10]]}},"alternative-id":["cells12192346"],"URL":"https:\/\/doi.org\/10.3390\/cells12192346","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,9,25]]}}}