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The exact proportion of chain-centric TCRs in the native repertoire is currently unknown, as is their inclusion in the repertoires of different functional T cell subsets. Discovering these main issues will elucidate the origin of chain-centric clonotypes and greatly improve their detection in bulk repertoires. In this work, the frequency and abundance of clonotypes with the dominant-active \u03b1-chain TCR (TCR\u03b1), i.e., \u03b1-chain-centric clonotypes, were identified in the mouse repertoires of primarily activated effectors and reactivated memory cells specific to tumor alloantigens. Screening tests in vitro showed that \u03b1-chain-centric clonotypes were contained in both repertoires, indicating that \u03b1-chain centricity could be an inherent feature of some TCRs. In both repertoires, the proportions of such clonotypes were found to be 20% to 25% of clonotypes expanded during antigenic stimulation. Transduction of na\u00efve T cells with the individual dominant-active TCR\u03b1 from both repertoires generated cytotoxic effectors that specifically killed the cognate tumor cells in\u00a0vitro. This study confirmed previous findings that T cell modification with TCR\u03b1 of \u03b1-chain-centric clonotypes generated functionally active antigen-specific effectors. Clonotypes with the dominant-active TCR\u03b1 were actively involved in the primary allogeneic response. In contrast to primarily activated effectors, \u03b1-chain-centric memory clonotypes had the complementarity-determining region 3 (CDR3) with the unique physicochemical signature of shorter length, increased charge, and lower volume and polarity. Here, \u03b1-chain-centric memory clonotypes were proposed as promising candidates for adoptive TCR\u2013T cell therapy.<\/jats:p>","DOI":"10.34133\/csbj.0026","type":"journal-article","created":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T18:31:17Z","timestamp":1773426677000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark_01","source":"Crossref","is-referenced-by-count":0,"title":["The Abundance of \u03b1-Chain-Centric TCRs in the Mouse Repertoire of Primarily Activated Effectors and Reactivated Memory T Cells"],"prefix":"10.34133","volume":"35","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6912-5579","authenticated-orcid":true,"given":"Anastasiia","family":"Kalinina","sequence":"first","affiliation":[{"name":"N.N. 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Blokhin National Medical Research Center of Oncology, Ministry of Health of the Russian Federation, 115478 Moscow, Russia."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexandra","family":"Bruter","sequence":"additional","affiliation":[{"name":"N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of the Russian Federation, 115478 Moscow, Russia."},{"name":"Center for Precision Genome Editing and Genetic Technologies for Biomedicine, \rInstitute of Gene Biology, Russian Academy of Sciences, 119334 Moscow, Russia."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ludmila","family":"Khromykh","sequence":"additional","affiliation":[{"name":"N.N. 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