Methods for comparing the diversity of samples of the T cell receptor repertoire

Analysis of T cell receptor (TCR) data has become a crucial element in many studies aimed at better understanding the evolution of the T cell repertoire and the role of TCR diversity in immune responses. In this paper we focus on comparing the diversity between samples of the TCR repertoire. We discuss some of the limitations and potential problems inherent in some of the more popular approaches to comparing samples of the TCR repertoire and we suggest alternate methods that both avoid these problems and enrich the analysis of TCR data. Examples from published studies of the CD8+ T cell responses to the influenza A virus DbNP366 and DbPA224 epitopes in mice are used to demonstrate the implementation of these methods. One example involves a comparison between the central and effector memory T cell subsets, defined on the basis of CD62L expression, and the other examines changes in the TCR repertoire over time.