Ligands of Gamma Delta T Cell Antigen Receptors

描述(由申请人提供)：伽马/德尔塔T细胞是免疫系统中最不被了解的组成部分之一。虽然这些细胞似乎对宿主的免疫能力做出了独特的贡献，但在宿主生物学或病理学的背景下定义它们的功能一直是困难的。这在很大程度上是因为目前还不清楚伽马/德尔塔T细胞针对的是什么。此前，我们已经确定T10/T22是γ/Delta T细胞的天然配体。基于对这一系统的分析，我们推测在免疫应答过程中诱导或以其他方式调节的经典和其他非经典MHC分子是具有重要生物学意义的伽马/Delta T细胞配体。为了测试这一点，我们调查了具有经典和非经典MHC分子四聚体的小鼠。我们的初步结果表明，相当大的伽马/德尔塔T细胞群可以被鉴定为II类MHC，I-Ek，以及非经典MHC，CD1d和Qa-1。这表明相当一部分的伽马/德尔塔TCR谱是MHC或MHC类分子所特有的。此外，虽然与I-Ek结合的多肽可能对识别的特异性不重要，但与CD1d结合的糖脂和与Qa-1结合的多肽似乎主导了识别的特异性。我们将扩大这些研究的范围，包括使用更灵敏的脂质体染色试剂进行调查，并分析这些特定的伽马/Delta T细胞识别配体的性质。我们的目标是更好地了解Gamma/Delta TCR谱系，它被调控的方式，以及这些特异性在免疫反应的更大背景下的作用。

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.