The expanding role of systems immunology in decoding the T cell receptor repertoire

T cells play a crucial role in the immune system's defense against many infectious diseases, including persistent infections for which no effective vaccines currently exist. The T cell component of the adaptive immune system is highly complex involving a constantly evolving landscape of various inter-related T cell populations. These T cell populations are characterized by their phenotypic and functional properties as well as the collection, or repertoire, of T cell receptors (TCR) that mediate T cell recognition of antigenic peptides derived from pathogens. Understanding the various processes and factors that impact the development and evolution of the broader T cell repertoire available to recognize and respond to pathogens and the characteristics of antigen-experienced T cell repertoires associated with effective immune control of pathogens is critical to the rational design of T cell-based vaccines and therapies. In this article we discuss, using examples of recent research, the promise that systems immunology approaches, involving quantitative analysis and mathematical and computational modeling of immunological data, hold for decoding the complex TCR repertoire system in the current era of advancing technologies.