Bohemian T cell receptors: sketching the repertoires of unconventional lymphocytes

Summary Over the last several decades, novel populations of unconventional T cells have been identified; defined by an invariant (or nearly invariant) T cell receptor ( TCR ) with a fixed specificity to non‐canonical antigens and major histocompatibility ( MHC ) molecules, they form large, functionally monoclonal populations tasked with surveying for their specific antigens. With residence in both lymphoid and non‐lymphoid tissues coupled with their ability to rapidly produce a spectrum of cytokines and effector molecules, the unconventional T cells are poised as some of the first responders to infection/damage and are thought to provide critical coverage before more focused, conventional T cell responses are mobilized. However, new technologies for the measurement and characterization of TCR repertoires have identified an underappreciated amount of TCR diversity in the unconventional T cells. In many cases, the specificities of these diverse TCR s converge on the same or similar antigens as their invariant counterparts, while others have yet to be defined. Here, we will review the current knowledge of the TCR repertoires of unconventional T cells and discuss how repertoires might be used as a framework for their organization, and further our understanding of their role not only during an immune response, but also their contribution in maintaining homeostasis.