Ligands of Gamma Delta T Cell Antigen Receptors

描述（由申请人提供）：γ/δ T细胞是免疫系统中了解最少的组成部分之一。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。这在很大程度上是因为还不清楚γ/δ T细胞库是针对什么的。以前，我们已经确定T10/T22作为γ/δ T细胞的天然配体。基于对该系统的分析，我们假设经典和其他非经典MHC分子，其在免疫应答期间被诱导或以其他方式调节，是生物学上重要的γ/δ T细胞配体。为了验证这一点，我们调查了经典和非经典MHC分子四聚体的小鼠。我们的初步结果表明，相当大的群体的γ/δ T细胞可以识别与II类MHC，I-Ek，和非经典的MHC，CD 1d和Qa-1。这表明相当大部分的γ/δ TCR库对MHC或MHC样分子具有特异性。此外，虽然与I-E k结合的肽可能对识别的特异性不重要，但与CD 1d结合的糖脂和与Qa-1结合的肽似乎主导特异性。我们将扩展这些研究，包括更敏感的脂质体染色试剂的调查，并分析这些特定的γ/δ T细胞的配体识别的性质。我们的目标是更好地了解γ/δ TCR库，其调节方式以及这些特异性在免疫应答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.