Development of Antigen-specific T Cell Memory

抗原特异性 T 细胞记忆的发展

• 批准号: 7673903
• 负责人: Michael G. McHeyzer-Williams
• 金额: $ 39.85万
• 依托单位: SCRIPPS RESEARCH INSTITUTE, THE
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-09-30 至 2012-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7673903
• 关键词: Affinity; Antigens; B-Cell Activation; B-Cell Development; B-Lymphocytes; Binding; CD4 Positive T Lymphocytes; Cell physiology; Cell surface; Cells; Clonal Evolution; Communicable Diseases; Development; Effector Cell; Event; Evolution; Gene Expression; Helper-Inducer T-Lymphocyte; Immune; Immune response; Immune system; Immunity; Immunization; Location; Maintenance; Memory; Memory B-Lymphocyte; Modeling; Mus; Nature; Pathway interactions; Phenotype; Prevention; Proteins; Public Health; Reaction; Research Personnel; Role; Route; Shapes; Site; Specificity; Staging; Structure of germinal center of lymph node; System; T memory cell; Time; Transgenic Organisms; Vaccinated; Vaccination; Vaccine Adjuvant; Vaccine Design; Vaccines; Work; attenuated microorganism; base; cell growth; cytokine; design; in vivo; insight; lymph nodes; pathogen; programs; response

DESCRIPTION (provided by applicant): Protein vaccination is an effective public health initiative with demonstrable utility in the prevention of infectious. An effective immune response to protein antigen relies on the helper T cell regulated development of high-affinity B cell memory and its consolidation after the vaccine boost. The cognate control of B cell immunity requires a spectrum of specialized effector Th cell functions that are temporally and spatially separated in vivo, the subsequent development of antigen-specific Th cell memory and the regulated re-activation of B cell memory responses. Clonal selection underpins the evolution of adaptive immunity in the Th cell and B cell compartment. Our recent studies indicate a unique set of rules for antigen- specific Th cells that control clonal recruitment and cellular expansion in vivo. Sequential selection events based on TCR-pMHCII affinity thresholds shape TCR diversity and regulate clonal dominance in the Th cell compartment. We hypothesize that the differential strength of TCR recognition is also a major determinant in priming effector Th cell function, shaping the memory Th cell compartment and re-shaping the memory response to antigen recall. We will determine the how TCR recognition controls evolution of effector cell evolution and function over the primary response to protein vaccination (SA1). We will then examine the impact of TCR recognition on the development of antigen-specific Th cell memory and the capacity of memory Th cells to respond to antigen recall. Over the course of these studies, we will provide fundamental new insights into the mechanisms controlling adaptive immunity and help to define the best means to obtain long-lasting high affinity B cell immunity to protein antigens. Protein vaccination is an important and effective preventative public health initiative. Vaccinating against sub-components of pathogens is a safe approach to vaccine design. However, we still don't fully understand how the immune system responds to these challenges and how the system develops a memory for what its seen. Our work seeks to understand how the system works in order to design better vaccine that promote stronger, longer lasting protective immune memory.

描述（由申请人提供）：蛋白质疫苗接种是一项有效的公共卫生倡议，可在预防传染性方面证明效用。对蛋白质抗原的有效免疫反应取决于辅助T细胞调节高亲和力B细胞记忆的发育及其在疫苗增强后其巩固。 B细胞免疫的同源控制需要一系列专门的效应子TH在体内和空间分离的细胞功能，随后的抗原特异性TH细胞记忆的发展以及B细胞记忆反应的调节重新激活。克隆选择基于TH细胞和B细胞室中适应性免疫的演变。我们最近的研究表明，控制克隆募集和体内细胞膨胀的抗原特异性TH细胞的独特规则。基于TCR-PMHCII亲和力阈值的顺序选择事件塑造了TCR多样性，并调节了TH细胞室中克隆优势。我们假设TCR识别的差异强度也是启动效应子TH功能的主要决定因素，塑造了记忆TH细胞室并重新塑造了对抗原回忆的记忆响应。我们将确定TCR识别如何控制对蛋白质疫苗接种的主要反应（SA1）的效应细胞演化的演变。然后，我们将研究TCR识别对抗原特异性细胞记忆的发展的影响以及记忆TH细胞对抗原回忆的反应的能力。在这些研究的过程中，我们将提供有关控制适应性免疫力的机制的基本新见解，并有助于定义获得对蛋白质抗原的持久高亲和力B细胞免疫的最佳方法。蛋白质疫苗接种是一项重要有效的预防性公共卫生倡议。针对病原体的亚材料接种疫苗是一种安全的疫苗设计方法。但是，我们仍然不完全理解免疫系统如何应对这些挑战，以及该系统如何为其所看到的记忆发展。我们的工作试图了解系统的工作原理，以设计更好的疫苗，以促进更强大，更持久的保护性免疫记忆。