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

项目总结 T细胞库中的每个幼稚细胞都表达一种独特的T细胞受体(TCR)，使其能够识别 主要组织相容性(PMHC)分子背景下的多肽抗原。TCR-pMHC相互作用是 针对微生物感染和癌症的长寿适应性免疫的主要决定因素。PMHC的使用 四聚体用于鉴定和研究表达与其同源配体高亲和力的TCR的T细胞 对我们理解T细胞介导的免疫具有变革性。然而，他们的生产问题 而这些试剂未能检测到表达低亲和力TCR的T细胞，导致了对 我们对T细胞反应的了解。在这里，我们建议开发一种技术，可以很容易地用于制造 广泛的pMHC和检测T细胞表达与其同源pMHC低亲和力的TCR。

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.