T-cell receptor chain centricity in the primarily activated effectors and re-stimulated memory cells

Abstract

T cells, the adaptive immunity effectors, carry an antigen-recognizing T-cell receptor (TCR) that represents an αβ heterodimer. Functional dominance of one chain has been reported for a number of TCRs. This feature is called chain centricity. Today, it is unclear whether chain centricity is an inherent feature of some TCRs, and what mechanism underlies its development. The study aimed to determine the abundance of such receptors in the repertoire of primarily activated effectors and re-stimulated memory cells of mice specific to the allogeneic tumor antigens. The long-lived memory cells formed in the primary immune response in vivo were in vitro re-stimulated with the immunizing tumor cells. Primary effectors were obtained in vitro in the culture by stimulation of T cells of non-immunized mice with cells of the same allogeneic tumor. TCR libraries of effectors involved in the primary and secondary immune response were created by NGS sequencing. To identify chain-centric TCRs, 10 ТCRα variants were selected from each repertoire. T cells of intact mice were modified with individual TCR α-chain variants by transduction, with subsequent assessment of T cell proliferation under exposure to specific allogeneic stimulators. In vitro screening revealed 10% of chain-centric receptors in the primary effector pool, and the proportion of such TCRs in the repertoire of re-activated memory cells was 30%. Thus, chain centricity is an inherent property of some TCRs, but secondary antigenic stimulation can be a factor for selection of clonotypes with such receptors.