Characteristics of T Cell Receptors

T 细胞受体的特征

基本信息

批准号：
8536033
负责人：
Philippa C. Marrack
金额：
$ 40.97万
依托单位：
NATIONAL JEWISH HEALTH
依托单位国家：
美国
项目类别：
财政年份：
1982
资助国家：
美国
起止时间：
1982-05-01 至 2014-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8536033
关键词：
Affect Alleles Amino Acids Animals Antigens Autoantigens Autoimmune Diseases Autoimmunity Automobile Driving Avidity Behavior Binding Binding Sites Breeding Cells Characteristics Collection Evolution Frequencies Generic Drugs Genes Germ Lines Histocompatibility Immune response Individual Infection Infectious Agent Insulin-Dependent Diabetes Mellitus Invaded Knowledge Ligands Major Histocompatibility Complex Mature T-Lymphocyte Methods Mus Nature Nucleotides Organism Peptide Library Peptide/MHC Complex Peptides Positioning Attribute Process Property Protein Binding Proteins Reaction Regulatory T-Lymphocyte Rheumatoid Arthritis Site Specificity Speed Structure T cell response T-Cell Receptor T-Lymphocyte TCR Activation Thymus Gland Time Tissues Transgenes Transgenic Organisms Ursidae Family Vaccines Work autoreactivity base design improved in vivo interest man member prevent receptor research study

项目摘要

DESCRIPTION (provided by applicant): T cells bearing ¿¿ T cell receptors (TCRs) are responsible for driving specific immune responses against invading organisms and, in the case of autoimmunity, against self. The TCRs on these cells react with antigenic peptides bound to major histocompatibility complex proteins (MHC). The reasons for the bias of TCRs for interaction with MHC has long been debated, however, recent evidence suggests that evolution has selected for amino acids at certain positions on TCRs that have a built in likelihood of engaging MHC. This project will investigate the nature of the sites on MHC that are the reciprocal of those on TCRs, i.e. that consistently engage the evolutionarily selected MHC-reacting amino acids of TCRs. Although evidence suggests that TCRs have the ability to react generically with MHC, individual TCRs are certainly specific for particular MHC proteins, as witnessed by the MHC allele restriction conferred on T cells during positive selection in the thymus. This project will study the structural bases for MHC allele specificity on the part of T cells. Regulatory T cells prevent immune responses against certain tissues in the body. It is thought that they do this by reacting with MHC bound to self peptides that are present in the tissue at issue. In spite of much work, little is known about the endogenous peptides that are recognized in normal mice by endogenous regulatory T cells. Mice and methods developed in this Project will be used, in conjunction with MHC/peptide libraries, to identify self peptides tha are recognized by regulatory T cells in normal mice. Overall, this Project will investigate various aspects of the TCR/MHC/peptide interaction. It will thus provide a firmer basis for our understanding of the structural bases for TCR interaction with generic and particular MHC proteins and illuminate the long mysterious process of T cell positive selection. Studies will also establish the nature of self peptides recognized in association with MHC by regulatory T cells, a discovery which will help understanding of the mode of action of regulatory T cells and perhaps improve ability to manipulate these cells in vivo.

描述（由应用程序提供）：带有T细胞接收器（TCR）的T细胞负责推动针对入侵生物的特定免疫反应，并且在自身免疫性的情况下，针对自我。这些细胞上的TCR与与主要组织相容性复合蛋白（MHC）结合的抗原性辣椒反应。但是，TCR与MHC相互作用的偏差的原因长期以来一直在争论，但是最近的证据表明，在TCR上某些位置的氨基酸选择了具有内置可能参与MHC的TCR的氨基酸。该项目将研究MHC上的位点的性质，而MHC是TCR上的倒数的，即始终参与TCRS的进化选择的MHC反应氨基酸。尽管有证据表明TCR具有一定能够与MHC反应的能力，但单个TCR当然对于特定的MHC蛋白是特异性的，如MHC等位基因限制在胸腺阳性选择期间赋予T细胞的MHC等位基因限制所见。该项目将研究T细胞中MHC等位基因特异性的结构碱基。调节性T细胞可防止对体内某些组织的免疫反应。人们认为，他们通过与MHC与有争议的组织中存在的自辣椒的反应来做到这一点。尽管有很多工作，但对于内源性调节T细胞在正常小鼠中识别的内源性胡椒却知之甚少。该项目中开发的小鼠和方法将与MHC/肽文库结合使用，以鉴定正常小鼠的调节T细胞识别自辣椒Tha。总体而言，该项目将调查各种 TCR/MHC/肽相互作用的各个方面。因此，它将为我们理解与通用和特定MHC蛋白相互作用的结构碱基，并阐明T细胞阳性选择的长期神秘过程。研究也将建立通过调节T细胞与MHC识别的自肽的性质，这一发现将有助于了解调节性T细胞的作用方式，并可能提高在体内操纵这些细胞的能力。