NON H-2 HISTOCOMPATIBILITY GENES AND ANTIGENS

小鼠次要组织相容性(H)抗原来源于天然 在不同品系的小鼠中碰巧具有抗原性的蛋白质 因为它们是多态的。它们是异基因移植的重要障碍 组织移植，并构成一个现实的模型系统 了解免疫系统如何处理天然蛋白质，表达 在生理水平，在正常和病理状态下。目标是 这项拟议的研究的目的是阐明 在体内测定对微小H抗原的免疫反应。的产品 某些微小的H基因选择性地刺激CD8+T细胞，而产物 刺激CD4T细胞。这种差异化刺激是一种 免疫反应的关键因素，因为成熟的CD8+细胞功能 由于细胞毒性T(TC)细胞和成熟的CD4+细胞主要功能是 辅助T(Th)细胞。我们的第一个目标是确定为什么 微小的H基因刺激不同的T细胞亚群。我们将决定 导致微小H抗原呈递的主要途径是否 刺激Th细胞是MHC体内微小H蛋白的转移 II类阴性细胞转化为抗原提呈细胞。这些研究将 阐明自身抗原是如何被呈现给 体内的免疫系统。我们还将确定Minor H的产品是否 基因刺激不同的T细胞亚群是因为免疫原肽 从它们派生出来的只有有限数量的MHC 同种异型。我们的第二个目标是确定 信号2(即，HELP)可以在对微小H抗原的Tc反应中传递 在活体内。我们将研究不同类型的细胞在分娩过程中的作用 我们还将检查各种自身免疫性疾病和 环境获得性微生物向c细胞传递信号2 体内对微小H抗原的反应。这些研究将澄清 可以确定TC免疫力的刺激类型，也可能打开 关于明显无关的免疫反应如何产生的新实验方向 可以相互影响。

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.