دورية أكاديمية
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Physiological and Functional Effects of Dominant Active TCRα Expression in Transgenic Mice.

التفاصيل البيبلوغرافية
العنوان: Physiological and Functional Effects of Dominant Active TCRα Expression in Transgenic Mice.
المؤلفون: Kalinina AA; N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of the Russian Federation, Kashirskoe sh., 24, 115478 Moscow, Russia., Ziganshin RK; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho-Maklaya st. 16/10, 117997 Moscow, Russia., Silaeva YY; Institute of Gene Biology, Russian Academy of Sciences, Vavilova st. 34/5, 119334 Moscow, Russia., Sharova NI; National Research Center, Institute of Immunology Federal Medical-Biological Agency of Russia, Kashirskoe sh., 24, 115522 Moscow, Russia., Nikonova MF; National Research Center, Institute of Immunology Federal Medical-Biological Agency of Russia, Kashirskoe sh., 24, 115522 Moscow, Russia., Persiyantseva NA; N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of the Russian Federation, Kashirskoe sh., 24, 115478 Moscow, Russia., Gorkova TG; N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of the Russian Federation, Kashirskoe sh., 24, 115478 Moscow, Russia., Antoshina EE; N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of the Russian Federation, Kashirskoe sh., 24, 115478 Moscow, Russia., Trukhanova LS; N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of the Russian Federation, Kashirskoe sh., 24, 115478 Moscow, Russia., Donetskova AD; National Research Center, Institute of Immunology Federal Medical-Biological Agency of Russia, Kashirskoe sh., 24, 115522 Moscow, Russia., Komogorova VV; National Research Center, Institute of Immunology Federal Medical-Biological Agency of Russia, Kashirskoe sh., 24, 115522 Moscow, Russia., Litvina MM; National Research Center, Institute of Immunology Federal Medical-Biological Agency of Russia, Kashirskoe sh., 24, 115522 Moscow, Russia., Mitin AN; National Research Center, Institute of Immunology Federal Medical-Biological Agency of Russia, Kashirskoe sh., 24, 115522 Moscow, Russia., Zamkova MA; N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of the Russian Federation, Kashirskoe sh., 24, 115478 Moscow, Russia.; Institute of Gene Biology, Russian Academy of Sciences, Vavilova st. 34/5, 119334 Moscow, Russia., Bruter AV; N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of the Russian Federation, Kashirskoe sh., 24, 115478 Moscow, Russia.; Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Institute of Gene Biology, Russian Academy of Sciences, 34/5 Vavilov St., 119334 Moscow, Russia., Khromykh LM; N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of the Russian Federation, Kashirskoe sh., 24, 115478 Moscow, Russia., Kazansky DB; N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of the Russian Federation, Kashirskoe sh., 24, 115478 Moscow, Russia.
المصدر: International journal of molecular sciences [Int J Mol Sci] 2023 Mar 30; Vol. 24 (7). Date of Electronic Publication: 2023 Mar 30.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Basel, Switzerland : MDPI, [2000-
مواضيع طبية MeSH: T-Lymphocytes* , Receptors, Antigen, T-Cell, alpha-beta*, Mice ; Animals ; Mice, Transgenic ; Receptors, Antigen, T-Cell/genetics ; Receptors, Antigen, T-Cell/metabolism ; Lymphocytes/metabolism
مستخلص: A T cell receptor (TCR) consists of α- and β-chains. Accumulating evidence suggests that some TCRs possess chain centricity, i.e., either of the hemi-chains can dominate in antigen recognition and dictate the TCR's specificity. The introduction of TCRα/β into naive lymphocytes generates antigen-specific T cells that are ready to perform their functions. Transgenesis of the dominant active TCRα creates transgenic animals with improved anti-tumor immune control, and adoptive immunotherapy with TCRα-transduced T cells provides resistance to infections. However, the potential detrimental effects of the dominant hemi-chain TCR's expression in transgenic animals have not been well investigated. Here, we analyzed, in detail, the functional status of the immune system of recently generated 1D1a transgenic mice expressing the dominant active TCRα specific to the H2-K b molecule. In their age dynamics, neither autoimmunity due to the random pairing of transgenic TCRα with endogenous TCRβ variants nor significant disturbances in systemic homeostasis were detected in these mice. Although the specific immune response was considerably enhanced in 1D1a mice, responses to third-party alloantigens were not compromised, indicating that the expression of dominant active TCRα did not limit immune reactivity in transgenic mice. Our data suggest that TCRα transgene expression could delay thymic involution and maintain TCRβ repertoire diversity in old transgenic mice. The detected changes in the systemic homeostasis in 1D1a transgenic mice, which are minor and primarily transient, may indicate variations in the ontogeny of wild-type and transgenic mouse lines.
Competing Interests: The authors declare no conflicts of interest.
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معلومات مُعتمدة: 22-15-00342 Russian Science Foundation
فهرسة مساهمة: Keywords: TCR repertoire; aging; allogeneic immune response; chain-centric TCR; dominant active TCRα; proteomics; thymic involution; transgenesis; transgenic mice
المشرفين على المادة: 0 (Receptors, Antigen, T-Cell, alpha-beta)
0 (Receptors, Antigen, T-Cell)
تواريخ الأحداث: Date Created: 20230413 Date Completed: 20230414 Latest Revision: 20230415
رمز التحديث: 20230415
مُعرف محوري في PubMed: PMC10094918
DOI: 10.3390/ijms24076527
PMID: 37047500
قاعدة البيانات: MEDLINE
الوصف
تدمد:1422-0067
DOI:10.3390/ijms24076527