Development of Cellular Tools and Techniques to Identify Low Affinity T Cells

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PROJECT SUMMARY Each naïve 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.