Each nave cell within the T cell repertoire expresses a unique T cell receptor (TCR) that allows it to recognize peptide antigens in the context of major histocompatibility (pMHC) molecules. TCR-pMHC interactions are the chief determinants of long-lived adaptive immunity against microbial infections and cancer. The use of pMHC tetramers to identify and study T cells expressing TCRs of high affinity for their cognate ligand has been transformational for our understanding of T cell-mediated immunity. However, problems with their production and a failure of these reagents to detect T cells expressing low affinity TCRs have led to significant limits on our knowledge of T cell responses. Here we propose to develop a technique that can be readily used to make a broad range of pMHC and detect T cells expressing TCRs of low affinity for their cognate pMHC.
T cells are an essential component of vertebrate immunity. Our understanding of these cells has been transformed by the use of pMHC tetramers, which allow for the detection T cells that bind their antigen with high affinity, but low affinity T cells remain out of reach of tetramer analysis. This proposal is aimed at developing tools and techniques that will make low affinity T cells accessible to most research labs.
