The Public Face and Private Lives of T Cell Receptor Repertoires

The emergence of next-generation sequencing (NGS)-generated T cell receptor repertoire data has allowed an in-depth look at the diversity of receptor sequences with a previously unobtainable resolution. These and other data have demonstrated a surprisingly high degree of shared or “public” TCRs at paired and single chain levels found in multiple individuals. Given the vast potential diversity of the naive repertoire, this apparently high level of degeneracy suggests one or more non-random mechanisms shaping receptor recombination and selection. One prominent hypothesis to address this phenomenon is convergent recombination, with public receptors being easier to generate through multiple recombination mechanisms. Associations between public and private responses and multiple T cell parameters, including immune efficacy, pathogenicity, and magnitude, have been explored in many experimental systems. Here, we review the case for functional associations with public and private repertoires, their mechanisms of generation, and the implications for future studies of the T cell repertoire. The utility of this distinction in research and diagnostic settings is also discussed.