Regulation and mechanism of agonist selection

激动剂选择的调控和机制

• 批准号: 7476462
• 负责人: HILDE MC CHEROUTRE
• 金额: $ 40.56万
• 依托单位: LA JOLLA INSTITUTE FOR IMMUNOLOGY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-08-05 至 2009-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7476462
• 关键词: Affinity; Agonist; Antigen-Presenting Cells; Antigens; Applications Grants; Autoantigens; Autoimmune Diseases; Automobile Driving; Cell Survival; Cell surface; Cells; Condition; Decision Making; Development; Ectopic Expression; Effector Cell; Fluorescence Resonance Energy Transfer; Immune; Immune system; Lead; Ligands; Malignant Neoplasms; Mature Thymocyte; Mediating; Mediator of activation protein; Molecular; Outcome; Pathway interactions; Play; Process; Regulation; Role; Self Tolerance; Signal Transduction; T-Lymphocyte; T-Lymphocyte and Natural Killer Cell; Technology; Testing; Thymus Gland; antigen processing; base; cell type; imprint; improved; insight; intraepithelial; novel; receptor; thymocyte

DESCRIPTION (provided by applicant): Positive selection of T cells by self-agonists or agoniselection, is a novel thymic selection process that directs the development of specialized T lymphocytes with regulatory functions. This selection process occurs concurrently with negative selection of autoreactive conventional TCRa¿ T cells and may be an important contributor in establishing self-tolerance. The total opposite outcome of the self-reactive immature thymocyte developing along the agonist selection pathway as opposed to the negative selection pathway suggests profound differences in the mediators that direct these two selection processes. The grant proposal aims at identifying and characterizing key factors that are crucial in this decision-making by examining the immature thymocytes, the selecting non-T cells and the crosstalk between these two cell types. Elucidating the conditions and requirements that lead to the specific selection of self-based regulatory T cells, as well as defining mechanisms that permit such selection, are fundamental for our understanding of how the immune system provides protection at all levels. New insights gained from this study will most certainly have important implications for understanding immune regulation and as a consequence for the development of new and improved immune-based therapies against cancer and autoimmune disorders.

描述（由申请人提供）：通过自身激动剂或激动剂选择对 T 细胞进行阳性选择，是一种新颖的胸腺选择过程，可指导具有调节功能的专门 T 淋巴细胞的发育，该选择过程与自身反应性常规 TCRa 的阴性选择同时发生。 T 细胞可能是建立自我耐受的重要贡献者，沿着激动剂选择途径而不是负选择途径发育的自我反应性未成熟胸腺细胞的完全相反的结果表明指导这两个选择过程的介质存在巨大差异。该拨款提案旨在通过检查未成熟胸腺细胞、选择非 T 细胞以及这两种细胞类型之间的串扰来识别和表征在这一决策中至关重要的关键因素。 阐明导致基于自身的调节性 T 细胞的特定选择的条件和要求，以及定义允许这种选择的机制，对于我们理解免疫系统如何在各个层面提供保护至关重要。这项研究肯定会对理解免疫调节产生重要影响，从而对开发新的和改进的针对癌症和自身免疫性疾病的免疫疗法产生重要影响。