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.

项目总结