NON H-2 HISTOCOMPATIBILITY GENES AND ANTIGENS

小鼠次要组织相容性（H）抗原来源于天然的 这些蛋白质在不同品系的小鼠中恰好具有抗原性， 因为它们是多态的。 它们是同种异体移植的重要障碍。 组织移植，并构成现实的模型系统， 了解免疫系统如何处理天然蛋白质， 在生理水平上，在正常和病理状态下。 客观 这项研究的目的是阐明基本的细胞机制， 测定体内对次要H抗原的免疫应答。 的产品 某些次要H基因选择性刺激CD8+ T细胞，而产物 另一些则刺激CD4 T细胞。 这种差异刺激是一种 免疫反应的关键因素，因为成熟的CD8+细胞的功能 因为细胞毒性T（Tc）细胞和成熟的CD4+细胞主要作为 辅助性T（Th）细胞。 我们的第一个目标是确定为什么 小H基因刺激不同的T细胞亚群。 我们将确定 是否是导致次要H抗原呈递的主要途径， 刺激Th细胞是从MHC转移体内次要的H蛋白 II类阴性细胞转化为抗原呈递细胞。 这些研究将 阐明自身抗原如何被呈递给 体内免疫系统。 我们还将确定次要H的产品是否 基因刺激不同的T细胞亚群， 来自它们的只有有限数量的MHC 同种异型 我们的第二个目标是确定 信号2（即，帮助）可以在对次要H抗原的Tc应答中递送 in vivo. 我们将研究不同类型的细胞在传递中的作用， 信号2 我们还将检查各种自身免疫性疾病和 环境获得的微生物将信号2传递给c细胞 在体内对次要H抗原的应答。 这些研究将阐明 可以决定Tc免疫力的刺激类型，也可能打开 新的实验方向，以了解明显无关的免疫反应 可以互相影响。

Murine minor histocompatibility (H) antigens are derived from natural proteins that happen to be antigenic among different strains of mice because they are polymorphic. They are significant barriers to allogeneic tissue transplantation and constitute a realistic model system for understanding how the immune system deals with natural proteins, expressed at physiological levels, in normal and pathological states. The objective of the proposed research is to elucidate the basic cellular mechanisms that determine immune responses to minor H antigens in vivo. The products of certain minor H genes selectively stimulate CD8+ T cells, whereas products of others stimulate CD4 T cells. This differential stimulation is a critical element of the immune response because mature CD8+ cells function as cytotoxic T (Tc) cells and mature CD4+ cells function primarily as helper T (Th) cells. Our first objective is to determine why products of minor H genes stimulate different T cell subsets. We will determine whether the major avenue leading to presentation of minor H antigens that stimulate Th cells is the transfer of minor H proteins in vivo from MHC class II-negative cells to antigen presenting cells. These studies will clarify athe dynamics of how self-antigens come to be presented to the immune system in vivo. We will also determine whether products of minor H genes stimulate deferent T cell subsets because immunogenic peptides derived from them are presented by only a restricted number of MHC allotypes. Our second objective is to determine the avenues by which Signal 2 (i.e., help) can be delivered in Tc responses to minor H antigens in vivo. We will examine the role of different cell types in the delivery of Signal 2. We will also examine whether various autoimmune disorders and environmentally-acquired microorganisms deliver Signal 2 to c cell responses against minor H antigens in vivo. These studies will clarify the types of stimuli that can determine Tc immunity and are also likely to open new experimental directions into how apparently unrelated immune responses can affect one another.