SOLUBLE T CELL RECEPTOR STUDIES ON MHC RESTRICTIONS

MHC 限制的可溶性 T 细胞受体研究

• 批准号: 2179844
• 负责人: NICHOLAS R GASCOIGNE
• 金额: $ 20.71万
• 依托单位: SCRIPPS RESEARCH INSTITUTE, THE
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-02-01 至 1999-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2179844
• 关键词: MHC class I antigen; T cell receptor; antigen presentation; biological signal transduction; biosensor device; cell differentiation; intermolecular interaction; ovalbumin; recombinant proteins; thymus

DESCRIPTION (Adapted from the applicant's abstract): Recognition of antigen by T cells involves an interaction between parts of the T cell receptor and an antigenic complex of self-major histocompatibility complex protein and peptide derived from a foreign protein. This interaction is of relatively weak affinity. In this project, soluble forms of the T cell receptor will be produced and used to measure the interaction. The ligand in question is a purified soluble form of the MHC class I protein, bound to an individual specific peptide. The interaction will be measured using surface plasmon resonance techniques. Previous studies have identified analogues of the peptide antigen that are antagonistic to the antigenic peptide. In addition, peptides that produce positive and negative selection in the thymus have been identified. The residues of the antigenic peptide that are important for interaction with the MHC and with the T cell receptor have been determined. Comparison will be made between the affinity of the TCR for MHC with these antigen analogues, in order to determine the role of affinity in activation of T cells, and in maturation of T cells in the thymus. This will give information on how the development or activation of T cells can be modulated by specific peptides, which may prove useful in prophylaxis or treatment of autoimmune disorders. Recognition of ligand by the T cell receptor results in initiation of a signaling cascade that activates the T cell. It is now known how this pathway is initiated by the receptor. The recognition event is transmitted in some way to other parts of the TCR complex, the CD3 molecules. This project will show to what extent TCR signaling is a qualitative or quantitative event.

描述（改编自申请人摘要）： T细胞对抗原的免疫反应涉及T细胞各部分之间的相互作用 受体和自身主要组织相容性抗原复合物 复合蛋白质和源自外源蛋白质的肽。 这 相互作用的亲和力相对较弱。 在这个项目中， T细胞受体的形式将被产生并用于测量 互动 所讨论的配体是一种纯化的可溶形式的 MHC I类蛋白，与单个特异性肽结合。 的 将使用表面等离子体共振技术测量相互作用。 先前的研究已经鉴定出肽抗原的类似物， 对抗原肽有拮抗作用。 此外， 在胸腺中产生正选择和负选择， 鉴定 抗原肽的重要残基 与MHC和T细胞受体相互作用的研究已经 测定 将在TCR对CD34 + T细胞的亲和力与CD34 + T细胞的亲和力之间进行比较。 MHC与这些抗原类似物，以确定其作用。 在T细胞活化中的亲和力，以及在T细胞成熟中的亲和力。 胸腺 这将提供有关如何开发或激活 可以通过特定的肽来调节T细胞，这可能证明是有用的。 预防或治疗自身免疫性疾病。 承认 配体通过T细胞受体导致信号传导的启动。 激活T细胞的级联反应。 现在已经知道这条途径是如何 由受体启动。 识别事件在一些实施例中被传输。 TCR复合物的其他部分，CD3分子。 这个项目 将显示TCR信号传导在多大程度上是定性或定量的 活动