ANALYSIS OF THE T CELL REPERTOIRE

T 细胞库分析

• 批准号: 3813463
• 负责人: R J HODES
• 金额: --
• 依托单位: DIVISION OF CANCER BIOLOGY AND DIAGNOSIS
• 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/3813463
• 关键词: T cell receptor; T lymphocyte; alleles; athymic mouse; biological polymorphism; clone cells; gene expression; histocompatibility antigens; laboratory mouse; leukocyte activation /transformation; ligands; linkage mapping; minor histocompatibility loci

An analysis of T cell receptor (TCR) expression in Mlsc reactive T cells demonstrated a striking association of this reactivity with expression of the Vbeta3 gene product. In addition, it was demonstrated that mouse strains which express Mlsc delete expression of Vbeta3 in their mature peripheral T cell populations. This failure to express Vbeta3 presumably reflects a consequence of the maintenance of tolerance to self Mlsc products. These findings provide a basis for the understanding of high T cell precursor frequency for Mlsc products, reflecting the overall expression of Vbeta3 in the T cell repertoire. Moreover, they demonstrate the importance of these products in selection of the antigen-specific T cell repertoire. The range of self antigens that influence Vbeta usage was evaluated by studying the expression of 16 Vbeta families in inbred mouse strains. Significant decreases in expression occurred in 8 of the 16 Vbeta families. The self ligands responsible for these deletions appeared to consist of both MHC encoded and non-MHC encoded components. These results demonstrate that strain specific decrease in VA expression occur in a major portion of the T cell repertoire and that a number of self-MHC and non-MHC products induced these deletions in the process of eliminating self reactivate T cells from the mature T cell pool. Studies employing athymic nude mice demonstrated that Vbeta deletions associated with self tolerance failed to occur in athymic mice, demonstrating that the thymus has a critical mediating self tolerance by negative selection.

MLSC反应性T细胞的T细胞受体(TCR)表达分析 证明了这种反应性与表达 Vbeta3基因产物。此外，还证明了小鼠 表达MLSC的菌株在成熟过程中Vbeta3的表达缺失 外周T细胞亚群。这种未能表达Vbeta3的现象可能 反映了对自身MLSC的容忍度保持的结果 产品。这些发现为理解高温高压提供了基础。 MLSC产品的细胞前体频率，反映了总体 Vbeta3在T细胞库中的表达此外，他们还展示了 这些产物在抗原特异性T细胞筛选中的重要性 细胞谱系。 影响Vbeta使用的自身抗原范围通过以下方法评估 研究16个Vbeta家族在近交系小鼠中的表达。 在16个Vbeta家族中，有8个家族的表达显著降低。 负责这些缺失的自体配体似乎包括 MHC编码的分量和非MHC编码的分量。这些结果表明 这种菌株特异性的VA表达下降发生在很大一部分 T细胞谱系和一些自身MHC和非MHC产物 在消除自我复活T细胞的过程中导致这些缺失 成熟T细胞池中的细胞。 利用裸鼠进行的研究表明，Vβ缺失 与自身耐受性相关的在无菌小鼠中未能发生， 证明胸腺具有关键的调节自身耐受性的作用 消极选择。