Comparative analysis of murine T‐cell receptor repertoires

On the way of understanding the rules and laws of adaptive immunity, high-throughput profiling of TCR repertoires becomes a powerful tool. The structure of TCR repertoires is insightful and instructive even before antigen specificity of each particular receptor becomes available. It embodies information about the thymic and peripheral selection of T cells, about the readiness of an adaptive immunity to withstand new challenges, about the character, the magnitude, and the memory of immune response, and about the etiological and functional proximity of T cell subsets. Here, we describe our current analytical approaches for comparative analysis of murine TCR repertoires, and show several examples of how these approaches can be applied for particular experimental settings. We analyze the efficiency of different metrics used for estimation of repertoire diversity, repertoires’ overlap, V- and J-gene segments usage similarity, and amino acid composition of CDR3. We discuss basic differences of these metrics, their advantages and limitations in different experimental models, and provide guidelines for choosing an efficient way to lead a comparative analysis of TCR repertoires. Applied to the various known and newly developed mouse models, such analysis should allow to disentangle multiple sophisticated puzzles in adaptive immunity. This article is protected by copyright. All rights reserved.