Antigen-specificity measurements are the key to understanding T cell responses

Abstract

Antigen-specific T cells play a central role in the adaptive immune response and come in a wide range of phenotypes. T cell receptors (TCRs) mediate the antigen-specificities found in T cells. Importantly, high-throughput TCR sequencing provides a fingerprint which allows tracking of specific T cells and their clonal expansion in response to particular antigens. As a result, many studies have leveraged TCR sequencing in an attempt to elucidate the role of antigen-specific T cells in various contexts. Here, we discuss the published approaches to studying antigen-specific T cells and their specific TCR repertoire. Further, we discuss how these methods have been applied to study the TCR repertoire in various diseases in order to characterize the antigen-specific T cells involved in the immune control of disease.

Keywords: T cell; TCR; adaptive immunity; antigen-specificity; sequencing.

Figure 1

Methods to identify antigen-specificity. pMHC multimers allows the direct identification of antigen-specific T cells, while indirect methods rely on cytokine production, surface marker expression or cell proliferation upon in vitro stimulation. Created with BioRender.com.

Figure 2

Antigen-specific TCR repertoire using in vitro culture. Cells are stimulated with antigens or epitope pools. Only those clonotypes that expanded upon stimulation compared to ex vivo T cell samples across both replicates are analyzed further. The clonotypes are overlapped to obtain antigen-specific clonotypes. Clonotypes that expand in response to multiple unrelated stimuli are excluded.