CD8+ CTL RECOGNITION OF MHC CLASS 1

MHC 1 类的 CD8 CTL 识别

• 批准号: 6373153
• 负责人: JANET M CONNOLLY
• 金额: $ 30.8万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-09-30 至 2005-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6373153
• 关键词: CD8 molecule; MHC class I antigen; autoantigens; autoimmunity; cytotoxic T lymphocyte; genetically modified animals; laboratory mouse; leukocyte activation /transformation; lymphopoiesis; thymus; tissue /cell culture; tumor antigens; virus antigen

DESCRIPTION (Adapted from the Investigator's abstract): The hallmark of the immune system is the remarkable ability to discriminate between self and foreign proteins displayed as peptides bound to self-major histocompatibility complex (MHC) molecules. T lymphocytes acquire this ability during development in the thymus in which low avidity interactions between T-cell receptors (TCRs) and self-MCH/peptide result in positive selection. High avidity interactions in the thymus result in negative selection and deletion of potentially autoreactive T-cell repertoire that is self-tolerant and self-MHC restricted. TCR affinity, MHC/peptide density and co-receptor engagement contribute to the overall avidity of the interaction between T-cells and antigen presenting cell (APC). This avidity sets up a balance between positive and negative selection and establishes the activation requirements of peripheral T-cells. The overall goal of this application is to correlate the thymic selection environment with the functional phenotype of the peripheral CD8T cell repertoire. Specificity of peripheral CD8 T-cells. To do this they will alter class I expression or CD8 interaction during thymic development and determine how it affects the ability of peripheral CD8 T-cells to distinguish APC expressing different levels of class I/peptide complexes. To address these questions, unique MHC Class I transgenic mice that express a single class I allele will be engineered. Using these mice, the diversity of the CD8 T-cell repertoire selected by a single class I allele, in the absence of other class I molecules, will be characterized. These analyses will probe mechanisms of tolerance to self-antigens and avoidance of autoimmune responses. Furthermore these studies will determine factors influencing activation requirements of self-restricted responses to tumor antigens and infectious virus as well as how individual MHC alleles contribute to alloreactive responses and transplantation tolerance.

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