Ligands of Gamma Delta T Cell Antigen Receptors

Gamma Delta T 细胞抗原受体的配体

• 批准号: 6986206
• 负责人: Yueh-Hsiu Chien
• 金额: $ 38.1万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-12-01 至 2009-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6986206
• 关键词: CD antigens; MHC class II antigen; Orthomyxoviridae; T cell receptor; T lymphocyte; X ray crystallography; biological signal transduction; genetically modified animals; glycolipids; histocompatibility antigens; influenza; laboratory mouse; leukocyte activation /transformation; ligands; major histocompatibility complex; polymerase chain reaction; receptor binding; receptor expression; stainings

DESCRIPTION (provided by applicant): Gamma/delta T cells are one of the least understood components of the immune system. While these cells appear to contribute uniquely to host immune competence, it has been difficult to define their function in the context of host biology or pathology. This is largely because it is unclear what the gamma/delta T cell repertoire is directed against. Previously, we have identified T10/T22 as natural ligands of gamma/delta T cells. Based on the analysis of this system, we postulate that classical and other non-classical MHC molecules, which are induced or otherwise regulated during immune responses, are biologically important gamma/delta T cell ligands. To test this, we have surveyed mice with tetramers of classical and non-classical MHC molecules. Our preliminary results show that sizable populations ofgamma/delta T cells can be identified with the class II MHC, I-Ek, and the non-classical MHCs, CD1d and Qa-1. This suggests that considerable fraction of the gamma/delta TCR repertoire is specific for MHC or MHC-like molecules. Moreover, while the peptides bound to I-E k may not be important for the specificity of recognition, glycolipids bound to CD1d and peptides bound to Qa-1 seem to dominate the specificity. We will extend these studies to include surveys with more sensitive liposomal staining reagents and to analyze the nature of ligand recognition by these specific gamma/delta T cells. Our goal is to gain a better understanding of the gamma/delta TCR repertoire, the manner in which it is regulated and the role of these specificities in the larger context of an immune response.

描述（由申请人提供）：γ/δ T 细胞是免疫系统中最不为人所知的组成部分之一。虽然这些细胞似乎对宿主免疫能力有独特的贡献，但很难在宿主生物学或病理学的背景下定义它们的功能。这主要是因为尚不清楚 γ/δ T 细胞库针对的是什么。此前，我们已将 T10/T22 鉴定为 γ/δ T 细胞的天然配体。基于对该系统的分析，我们假设在免疫反应过程中被诱导或以其他方式调节的经典和其他非经典 MHC 分子是生物学上重要的 γ/δ T 细胞配体。为了测试这一点，我们对具有经典和非经典 MHC 分子四聚体的小鼠进行了调查。我们的初步结果表明，大量的 γ/δ T 细胞可以通过 II 类 MHC、I-Ek 和非经典 MHC、CD1d 和 Qa-1 进行鉴定。这表明相当一部分 γ/δ TCR 库对 MHC 或 MHC 样分子具有特异性。此外，虽然与 I-E k 结合的肽对于识别的特异性可能并不重要，但与 CD1d 结合的糖脂和与 Qa-1 结合的肽似乎在识别特异性中占主导地位。我们将扩展这些研究，包括使用更灵敏的脂质体染色试剂进行调查，并分析这些特定γ/δ T 细胞的配体识别性质。我们的目标是更好地了解 γ/δ TCR 指令、其调节方式以及这些特异性在免疫反应的更大背景下的作用。