Memory T cells: research experience of original models with transgenic T-cell receptors

This paper summarizes the experience of research conducted on original mouse models developed in the Laboratory of Regulatory Mechanisms in Immunity at the Carcinogenesis Institute of the N.N. Blokhin National Research Institute of Oncology of the Ministry of Health of the Russian Federation. The transgenesis of individual α- and β-chains of T-cell receptors (TCR) of memory cells led to the production of animal lines valuable for studies of T-lymphocyte homeostasis and patterns of formation of their activation marker profiles. The obtained models revealed new features of immune selection and tumor progression. With their help, a fundamental property of some TCRs, recently called chain centricity, was confirmed, which implies the functional dominance of one of the TCR chains during recognition of the MHC/peptide complex. This property allows to form significant pool of antigen-specific T cells, which can be used for the adoptive immunotherapy of oncological and infectious diseases. Transgenesis of dominant active TCR α-chains provides opportunities for the creation of organisms with innate specific immunological resistance to certain pathogens. The results of recent works indicate that TCR, by determining the relationship of the T-lymphocyte with its MHC microenvironment, has an instructive role in the formation of its functions and phenotype. One of these functions may be the production of cyclophilin A by cortisone-resistant memory cells localized in the thymus. There is accumulating evidence that expression of a TCR with a certain structure and specificity is a sufficient condition for the formation of the functional potential of memory cells in a T cell, regardless of the history of its interaction with antigenic MHC/peptide complexes.