VARIABLE GENE UTILIZATION IN SPECIFIC T CELL RESPONSES

特定 T 细胞反应中的可变基因利用

• 批准号: 2442227
• 负责人: MAURICE ZAUDERER
• 金额: $ 13.2万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-09-01 至 1998-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2442227
• 关键词: MHC class I antigen; SCID mouse; T cell receptor; T lymphocyte; Vesiculovirus; autoimmunity; cell differentiation; gene expression; leukocyte activation /transformation; molecular cloning; nucleoproteins; organ culture; ovalbumin; receptor binding; synthetic peptide; thymus

We have described an experimental model in which variant peptides are introduced in fetal thymic organ culture to determine whether they have the ability to promote differentiation of T cells of a defined specificity. Identification of a family of such peptides opens the possibility of directly addressing the relationship between MHC- associated peptides that select a mature T cell in the thymus and the particular foreign peptide that induces activation of this same T cell in the periphery. One widely discussed model suggests that reduced affinity of interaction between T cell receptor and an MHC:self-peptide complex could result in positive rather than negative selection in the thymus. In collaboration with David Margulies (Laboratory of Immunology, NIAID, NIH), we will exploit recent advances in the ability to engineer T cell receptor cDNA to facilitate isolation of soluble receptor molecules. We will then determine the relative affinity and kinetics of binding of purified TCR for complexes of soluble H-2Kb with either unmodified ligands or with the structurally related peptide analogs that were employed to positively select mature T cells that express this TCR.

我们描述了一个实验模型，其中变异肽 引入胎儿胸腺器官培养物以确定它们是否具有 促进特定 T 细胞分化的能力 特异性。此类肽家族的鉴定开启了 直接解决MHC-之间关系的可能性 选择胸腺中成熟 T 细胞的相关肽 诱导同一 T 细胞激活的特定外源肽 在外围。一种广泛讨论的模型表明，减少 T 细胞受体与 MHC:自身肽之间相互作用的亲和力 复杂的可能会导致正选择而不是负选择 胸腺。 与 David Margulies（免疫学实验室， NIAID、NIH），我们将利用工程能力的最新进展 T 细胞受体 cDNA 有助于分离可溶性受体 分子。然后我们将确定相对亲和力和动力学 纯化的 TCR 与可溶性 H-2Kb 复合物的结合 未修饰的配体或结构相关的肽类似物 用于阳性选择表达该 TCR 的成熟 T 细胞。

项目成果

Construction and characterization of vaccinia direct ligation vectors.

痘苗直接连接载体的构建和表征。

• 发表时间: 1997-11-24
• 作者: Merchlinsky, M;Eckert, D;Smith, E;Zauderer, M
• 通讯作者: Zauderer, M

Requirements for stimulation of autoreactive T cells by thymic stroma.

胸腺基质刺激自身反应性 T 细胞的要求。

• 发表时间: 1989-09-01
• 作者: Burstyn, D;Zauderer, M
• 通讯作者: Zauderer, M

Limiting dilution analysis of primary cytotoxic T-cell precursors.

原代细胞毒性 T 细胞前体的有限稀释分析。

• 发表时间: 1997-10-13
• 影响因子: 2.2
• 作者: Zauderer, M;Singer, A
• 通讯作者: Singer, A