Dominant role of the α-chain in rejection of tumor cells bearing a specific alloantigen in TCRα transgenic mice and in in vitro experiments.

Autor:	Zamkova M; 'N. N. Blokhin National Medical Research Centre of Oncology' of the Health Ministry of Russia, Moscow, Russia., Kalinina A; 'N. N. Blokhin National Medical Research Centre of Oncology' of the Health Ministry of Russia, Moscow, Russia., Silaeva Y; Institute of Gene Biology, Russian Academy of Sciences, Moscow, Russia., Persiyantseva N; 'N. N. Blokhin National Medical Research Centre of Oncology' of the Health Ministry of Russia, Moscow, Russia., Bruter A; Russian Academy of Sciences, Engelhardt Institute of Molecular Biology, Moscow, Russia., Deikin A; Institute of Gene Biology, Russian Academy of Sciences, Moscow, Russia., Khromykh L; 'N. N. Blokhin National Medical Research Centre of Oncology' of the Health Ministry of Russia, Moscow, Russia., Kazansky D; 'N. N. Blokhin National Medical Research Centre of Oncology' of the Health Ministry of Russia, Moscow, Russia.
Jazyk:	angličtina
Zdroj:	Oncotarget [Oncotarget] 2019 Aug 06; Vol. 10 (47), pp. 4808-4821. Date of Electronic Publication: 2019 Aug 06 (Print Publication: 2019).
DOI:	10.18632/oncotarget.27093
Abstrakt:	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-2K b 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-2K b 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-2K b -specific TCR to determine specific recognition of the H-2K b molecule by a repertoire of T lymphocytes and to rapidly reject H-2K b -bearing lymphoma cells. Competing Interests: CONFLICTS OF INTEREST The authors declare no commercial or financial conflicts of interest.
Databáze:	MEDLINE
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