Dominant role of the α-chain in rejection of tumor cells bearing a specific alloantigen in TCRα transgenic mice and in in vitro experiments
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Maria Zamkova1,*, Anastasiya Kalinina1,*, Yuliya Silaeva3,*, Nadezhda Persiyantseva1, Alexandra Bruter2, Alexey Deikin3, Ludmila Khromykh1 and Dmitry Kazansky1
1 “N. N. Blokhin National Medical Research Centre of Oncology” of the Health Ministry of Russia, Moscow, Russia
2 Russian Academy of Sciences, Engelhardt Institute of Molecular Biology, Moscow, Russia
3 Institute of Gene Biology, Russian Academy of Sciences, Moscow, Russia
* These authors contributed equally to this work
|Dmitry Kazansky,||email:||[email protected]|
Keywords: transgenic mice; TCRα; tumor; alloantigen
Received: March 12, 2019 Accepted: June 29, 2019 Published: August 06, 2019
Both TCRα and TCRβ types of T-cell receptors contribute to antigen recognition. However, some TCRs have chain centricity, which means that either the α-chain or the β-chain dictates the peptide–MHC complex specificity. Most earlier reports investigated the role of well-studied β-chains in antigen recognition by TCRαβ. In a previous study, we identified TCRs specific to the H-2Kb molecule. In the present work, we generated transgenic mice carrying the α-chain of this TCR. We found that these transgenic mice rejected EL-4 tumor cells bearing alloantigen H-2Kb more effectively than wild-type mice and similarly to mice with established specific memory T cells. Moreover, we found that T cells transduced with this TCRα can inhibit EL-4 cell growth in vitro and in vivo. We also found that transgenic mice recruit fewer CD8 T cells into the peritoneal cavity at the peak of the immune response and had a significantly higher number of central memory CD8 T cells in the spleen of intact transgenic mice compared to intact wild-type control. These results indicate the ability of a single transgenic α-chain of the H-2Kb-specific TCR to determine specific recognition of the H-2Kb molecule by a repertoire of T lymphocytes and to rapidly reject H-2Kb-bearing lymphoma cells.
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