Each individual harbours a vast and unique repertoire of immune receptors which discriminate, at the molecular level, self from non-self. Although the central importance of T cells in adaptive immunity has been well established for decades, the actual number and diversity of T cells that exist in an individual (i.e., the T cell repertoire), how this changes in response to immune challenge and how it varies from one individual to the next has remained unknown. Dr. Holt’s lab used deep sequencing to obtain a first glimpse of T cell repertoire diversity at the ultimate resolution of individual clonotypes (Freeman et al., Genome Res. 2009). Currently, the Holt Lab is using these methods to explore the role of T cells in cancer, and how to enhance the anti-cancer immune response. They are particularly focused on developing new sequence-based approaches to T cell antigen discovery and characterization.