MHC AND GAMMA/DELTA T-CELL RECOGNITION

伽玛德尔塔T细胞存在于各种脊椎动物体内。尽管 尽管进行了激烈的努力，但它们在免疫系统中的作用仍然难以捉摸。 虽然他们显然在一些病态的情况下占主导地位，但他们的 未能显著参与大多数免疫反应表明 它们独特而有效地执行某些功能，因此可以 对宿主免疫防御系统的贡献不同于Alphabeta T 细胞。为了更好地了解Gammadelta T细胞是如何 对于免疫能力，管理它们识别的规则需要 要被理解。特别是，虽然大多数Alphabeta T细胞识别 主要组织相容性基因背景下的加工抗原 复杂(MHC)分子，许多特异性Gammadelta T细胞没有 可演示的MHC限制。此外，尽管有 对MHC或MHC样分子具有同种特异性的Gammadelta T细胞， 它们的特殊性的许多方面表明了根本的不同 在Gammadelta T细胞和Alphabeta T细胞之间。 这里描述的研究的目的是通过以下方式澄清这些问题 详细分析了三个特征的精确性 不同的异基因反应性Gammadelta T细胞克隆。我们的目标是 了解：(I)当Gammadelta T细胞识别涉及MHC时 分子，无论MHC分子是否起到类似于 Alphabeta T细胞识别，(Ii)是否以及何种类型的抗原处理 是必需的，(Iii)MHC分子的哪一部分被识别， 如果识别出一个肽/MHC复合体，那么它的性质是什么？ 多肽，(Iv)这些规则有多普遍。 我们最初的关注点是第二类MHC同种反应性Gammadelta T细胞， LBK-5，即I-Ek，b，S反应性。我们将首先分析LBK-5 TCR/I-EK 与表达突变I-Ek的抗原提呈细胞(APC)的相互作用 分子，以及抗原处理要求将被用来探讨 APC在内吞途径中有缺陷。我们的初步结果表明 LBK-5与I-Ek的交互作用与任何Alphabeta非常不同 测试了T细胞，并且它有不同的抗原处理要求 也是。这些实验将得到确认和推广，并用作 确定配基的依据(S)。这些结果的一般性将 通过与其他同种异体反应性Gammadelta T细胞的平行研究进行检查 克隆，如LKD-1(I-Ad特异性)和G8(TLB特异性)。 清楚了解Gammadelta T细胞如何很好地识别这些细胞 所研究的分子将提供对Gammadelta T的本质的洞察 细胞特异性和帮助更好地确定它们在免疫中的作用 系统。

Gammadelta T cells are found in a variety of vertebrate animals. Despite intense efforts, their role in the immune system has remained elusive. While they are clearly dominant in a few pathological situations, their failure to be significantly involved in most immune responses suggests that they perform certain functions uniquely and efficiently and thus may contribute to host immune defense systems differently than alphabeta T cells. In order to better understand how gammadelta T cells contribute to immunological competence, the rules governing their recognition need to be understood. In particular, while most alphabeta T cells recognize processed antigens in the context of a major histocompatibility gene complex (MHC) molecule, many specific gammadelta T cells have no demonstratable MHC restriction. In addition, although there are gammadelta T cells with allospecificity to MHC or MHC-like molecules, many aspects of their specificity suggest a fundamental difference between gammadelta T cell and alphabeta T cells. The object of the research described here is to clarify these issues by analyzing in detail the precise nature of the specificity of three different alloreactive gammadelta T cell clones. Our goal is to understand: (i) When gammadelta T cell recognition involves a MHC molecule, whether or not the MHC molecule plays a similar role as in alphabeta T cell recognition, (ii) if and what type of antigen processing is required, (iii) which part of the MHC molecule is being recognized, and, if a peptide/MHC complex is recognized, what is the nature of the peptide, (iv) how general these rules are. Our initial focus is on the Class II MHC allo-reactive gammadelta T cell, LBK-5, which is I-Ek,b,s reactive. We will first analyze LBK-5 TCR/I-Ek interactions with antigen presenting cells (APC) expressing mutant I-Ek molecules, and the antigen processing requirements will be probed with APCs defective in the endocytic pathway. Our preliminary results suggest that LBK-5 interacts with I-Ek very differently than any of the alphabeta T cells tested, and that it has distinct antigen processing requirements as well. These experiments will be confirmed and extended, and used as a basis to identify the ligand(s). The generality of these results will be examined by parallel studies of other alloreactive gammadelta T cell clones, such as LKD-1 (I-Ad specific) and G8 (TLb specific). A clear understanding of how gammadelta T cells recognize these well studied molecules will provide insight into the nature of gammadelta T cell specificity and help to better define their role in the immune system.