Determining antigen recognition in systemic sclerosis

确定系统性硬化症中的抗原识别

• 批准号: 9915867
• 负责人: Michael Birnbaum
• 金额: $ 11.3万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/9915867
• 关键词: Antibodies; Antigens; Autoantigens; Autoimmune Process; B-Cell Activation; CD4 Positive T Lymphocytes; Cell Death; Clone Cells; Diffuse; Diffuse Scleroderma; Disease; Expression Library; Fibrosis; Goals; HLA-DPB1 gene; Helper-Inducer T-Lymphocyte; Human; IgG4; Inherited; Knowledge; Lead; Libraries; Link; Pathogenesis; Pathogenicity; Patients; Peptides; Principal Investigator; Process; Site; Systemic Scleroderma; T-Cell Receptor; T-Lymphocyte; Tissues; Type I DNA Topoisomerases; Yeasts; base; cytokine; cytotoxic; programs; receptor; single-cell RNA sequencing

PROJECT SUMMARY This project focuses on the identification of specific self-antigens that activate CD4+ T cells in systemic sclerosis. Cytotoxic CD4+T cells may directly contribute to cell death in tissues and secrete cytokines that lead to fibrosis. They likely receive help from activated B cells in tissues that in turn are induced by T follicular helper cells. Our goal is to use an unbiased approach to identify self antigens that activate clonally expanded cytotoxic CD4+T cells and/or T follicular helper cells from patients with diffuse systemic sclerosis who specifically have inherited HLA-DPB1*1301. Single cell cloning of CD4+ T cells will be used to identify matched T cell receptor alpha and beta chains from the most expanded cytotoxic CD4+ T cells and T follicular helper cells. Soluble T cell receptors will be generated. These soluble receptors will be used to screen a library of all human self peptides fused to HLA-DPB1*1301 and expressed in yeast.

项目概要 该项目的重点是识别激活 CD4+ T 的特定自身抗原 系统性硬化症中的细胞。细胞毒性 CD4+T 细胞可能直接导致细胞死亡 组织并分泌导致纤维化的细胞因子。他们可能会得到激活的帮助 组织中的 B 细胞又由滤泡辅助 T 细胞诱导。我们的目标是使用一个 识别激活克隆扩增细胞毒性的自身抗原的公正方法 来自弥漫性系统性硬化症患者的 CD4+T 细胞和/或滤泡辅助性 T 细胞 明确遗传了 HLA-DPB1*1301 的人。 CD4+ T 细胞的单细胞克隆将 用于从大多数 T 细胞受体 α 和 β 链中识别匹配的 T 细胞受体 α 和 β 链 扩增的细胞毒性 CD4+ T 细胞和滤泡辅助 T 细胞。可溶性T细胞受体 将被生成。这些可溶性受体将用于筛选所有人类的文库 与 HLA-DPB1*1301 融合并在酵母中表达的自身肽。