REVIEW: Memory T Cells: Investigation of Original Models with Transgenic T Cell Receptors

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Dmitry B. Kazansky^1,a*, Anastasiia A. Kalinina¹, Ludmila M. Khromykh¹

¹N. N. Blokhin National Medical Research Center of Oncology, Ministry of Health of the Russian Federation, 115522 Moscow, Russia

^* To whom correspondence should be addressed.

Received: October 31, 2024; Revised: December 26, 2024; Accepted: December 27, 2024

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This review summarizes the research data on original mouse models developed in the laboratory of regulatory mechanisms in immunity of the Research Institute of Carcinogenesis, N. N. Blokhin National Medical Research Center of Oncology, Ministry of Health of the Russian Federation. Transfer of the genes of individual α- and β-chains of T cell receptors (TCRs) of memory cells has resulted in production of transgenic animal lines valuable for studying T lymphocyte homeostasis and patterns of formation of their activation profile markers. Investigation of the transgenic models revealed new features of immune selection and tumor progression. In particular, the fundamental property of some TCRs, termed “chain-centricity”, has been confirmed; it involves dominance of one of the TCR chains during recognition of the MHC (major histocompatibility complex)/peptide complex. This property makes it possible to artificially generate a significant pool of immunocompetent T cells so it could be used in adoptive immunotherapy for oncological and infectious diseases. Transfer of the dominant active TCR α-chains provides the possibility for constructing organisms with innate specific immunological resistance to certain pathogens. The results of recent studies indicate that TCR, determining the T lymphocyte relationship with its MHC microenvironment, has an instructive role in formation of its functions and phenotype. One of these functions may be production of cyclophilin A by the cortisone-resistant memory cells localized in thymus. The evidence has been accumulated that expression of TCR with a certain structure and specificity is a sufficient condition for formation of the functional potential of memory cells in a T cell, regardless of its former interaction with antigenic MHC/peptide complexes.

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KEY WORDS: T lymphocyte, repertoire, major histocompatibility complex, peptide, thymus, T cell receptor, chain-centricity, cyclophilin A, transgenesis, adaptive immunity, adoptive immunotherapy

DOI: 10.1134/S0006297924603940

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