Characteristics of T Cell Receptors

T 细胞受体的特征

基本信息

批准号：
8761872
负责人：
Philippa C. Marrack
金额：
$ 41.02万
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 2019-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8761872
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 public health relevance 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 types and alleles of 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 that are recognized by regulatory T cells. Overall, this Project will investigate various aspects o 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 sel-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（由申请人提供）：T 细胞带有 ¿ ¿ T 细胞受体 (TCR) 负责驱动针对入侵生物体的特异性免疫反应，在自身免疫的情况下，还负责针对自身。这些细胞上的 TCR 与与主要组织相容性复合体蛋白 (MHC) 结合的抗原肽发生反应。 TCR 与 MHC 相互作用的偏见长期以来一直存在争议，然而，最近的证据表明，进化选择了 TCR 上某些位置上的氨基酸，这些位置具有与 MHC 相互作用的内在可能性。该项目将研究其性质。 MHC 上的位点与 TCR 上的位点相反，即始终参与 TCR 的进化选择的 MHC 反应氨基酸。和 MHC 蛋白的等位基因，正如胸腺正选择过程中 T 细胞受到的 MHC 等位基因限制所证明的那样，该项目将研究 MHC 等位基因特异性的结构基础。在 T 细胞的一部分，人们认为它们通过与相关组织中存在的自身肽发生反应来阻止针对某些组织的免疫反应。关于正常小鼠中内源性调节性 T 细胞识别的内源性肽知之甚少，本项目开发的方法将与 MHC/肽库结合使用，以鉴定被调节性 T 细胞识别的自身肽。总体而言，该项目将研究 TCR/MHC/肽相互作用的各个方面，这将为我们理解 TCR 与通用和特定 MHC 蛋白相互作用的结构基础提供更坚实的基础，并阐明 T 细胞正选择的长期神秘过程。确定调节性 T 细胞与 MHC 相关的自我肽的性质，这一发现将有助于理解调节性 T 细胞的作用模式，并可能提高体内操纵这些细胞的能力。