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

开发识别低亲和力 T 细胞的细胞工具和技术

基本信息

批准号：
9974912
负责人：
Michael S Kuhns
金额：
$ 23.03万
依托单位：
UNIVERSITY OF ARIZONA
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-09 至 2022-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9974912
关键词：
Adopted Affinity Antigen-Presenting Cells Antigens Baculoviruses Basic Science Benchmarking Binding Biological Assay CD4 Positive T Lymphocytes Cell Line Cells Cellular Immunity Cellular biology Communities Complex Coupled Coupling Data Detection Engineering Epitopes Failure Frequencies Gene Expression Profiling Generations Genetic Transcription Goals Histocompatibility Immunity Immunology Infection Insecta Knowledge Ligands Lymphoma Major Histocompatibility Complex Malignant Neoplasms Mammalian Cell Methods Molecular Biology OVA 323-339 Paper Peptide/MHC Complex Peptides Phenotype Population Process Production Protocols documentation Publishing Reagent Recombinants Research Research Personnel Research Proposals Stains Surveys T cell response T-Cell Immunologic Specificity T-Cell Receptor T-Lymphocyte Techniques Technology Testing Variant West Nile virus Work adaptive immunity cellular development cytokine design enzyme linked immunospot assay in vivo insight microbial monomer prevent response tissue culture tool

项目摘要

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.

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。