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ORIGINAL RESEARCH
Features of the immune response to tumor alloantigens in the context of decreased clonal diversity of T cells
Blokhin National Medical Research Center of Oncology, Ministry of Health of the Russian Federation, Moscow, Russia
Correspondence should be addressed: Dmitry B. Kazansky
Kashirskoe shosse, 24, str. 15, Moscow, 115478, Russia; ur.xednay@1yksnazak
Funding: the study was financially supported by the Russian Science Foundation grant No. 22-15-00342-П (https://rscf.ru/project/22-15-00342/).
Author contribution: Korotkova MS — experimental work, analysis of the results; Persiyantseva NA — experimental work, analysis of the results, article editing; Kalinina AA — study planning, analysis and interpretation of the results, analysis of the available literature, article authoring and editing; Khromykh LM — article editing; Kazansky DB — study planning, analysis and interpretation of the results, analysis of the available literature, article editing.
Compliance with ethical standards: the study was approved by the Ethics Committee of the N.N. Blokhin National Research Medical Center of Oncology of the Ministry of Health of the Russian Federation (Minutes No. 3-П10.06.2022 of June 10, 2022) and conducted in strict accordance with the provisions of Directive 2010/63/EU of the European Parliament and of the Council of 22 September 2010 on the protection of animals used for scientific purposes.
A T cell receptor (TCR), an αβ heterodimer, recognizes peptide antigens presented by self molecules of the major histocompatibility complex (MHC). A significant number of T cell clonotypes are alloreactive: they can interact with various allelic variants of MHC and the associated peptides. Currently, it is unclear whether the effectiveness of the allogeneic immune response depends on the diversity of the TCR repertoire. Seeking to experimentally narrow the diversity of T cell clonotypes, we used mice with transgenic expression of the β-chain TCR (TCRβ) in this work. We analyzed how the TCRß-transgenic mice on the CBA/Lac (H-2k) background respond to EL-4 (H-2Kb) lymphoma cells in vivo with the aim to assess the effect of a narrower repertoire on the allogeneic immune response. The study has shown that transgenic mice develop a weak immune response to transplant antigens, and the formed pool of cytotoxic T cells is 1.5–1.7-fold smaller than that in wild-type animals. Consequently, the mice failed to reject the allogeneic tumor, leading to 100% mortality rate. The results of this work are consistent with the data from our earlier studies that employed another TCRß-transgenic model. They confirm that the decreased diversity of the TCR repertoire impairs the response to alloantigens, allowing the tumor to evade the immune response and progress in the allogeneic recipient.
Keywords: T-cell receptor, T-cell, allogeneic response, decreased clonal diversity