Interrogating the relationship between naïve and immune antiviral T cell repertoires

•The complexity of TCR usage in antiviral T cell responses impacts on viral clearance.•Single cell PCR based methods are optimal for analysis of antigen-specific T cell repertoires.•Antiviral immune CTL repertoires broadly reflect the naïve CTL precursors from which they are derived.•Selective clonal expansion is routinely observed from naïve into immune antiviral CTL populations.•This selective expansion is likely driven by TCR avidity.

Understanding how naïve virus-specific CD8+ T cells influence the type of immune response generated after virus infection is critical for the development of enhanced therapeutic and vaccination strategies to exploit CD8+ T cell-mediated immunity. Recent technological advances in T cell isolation and T receptor sequencing have allowed for greater understanding of the basic structure of immune T cell repertoires, the diversity of responses within and between individuals, and changes in repertoires over time and in response to infection conditions. In this review, we discuss the current understanding of how T cell repertoires contribute to potent antiviral responses. Additionally we compare the state of the art in receptor sequencing, highlighting the advantages and disadvantages of the three most common approaches: next-generation sequencing, template-switch anchored RT-PCR, and multiplex single cell PCR. Finally, we describe how TCR sequencing has delineated the relationship between naïve and immune T cell repertoires.