Discovery of H. pylori T cell epitopes unique to minority populations that could contribute to increased gastric cancer rates.

幽门螺杆菌(Hp)是一种可以从人体内根除的细菌感染。 然而，抗生素的耐药性正在上升。这种病原体似乎在人类健康的消化过程中发挥了作用，因为 微生物组的一种成分，但也与溃疡、胃癌和 胃淋巴瘤。众所周知，幽门螺杆菌诱导的免疫炎症会增加患胃炎和 胃癌。在美国，患病率因地理位置、种族背景、 社会经济地位和年龄。例如，纳瓦霍民族成员和西班牙裔美国人的比例不成比例 与高加索人相比，胃癌的发病率很高。而胃癌与幽门螺杆菌有关 感染，为什么某些人群患胃癌的风险增加并不完全是 明白了。已发表的研究表明，幽门螺杆菌变异、人类MHC类型和T细胞反应在 炎症和胃炎。然而，对幽门螺杆菌变异和人类MHC如何存在的调查 不同的多肽对免疫系统的影响还没有大规模的研究。这项建议旨在 通过检测幽门螺杆菌在原住民中的遗传变异来研究这种传染病-慢性病的界面 居住在亚利桑那州北部和西班牙裔的美国人，普通原住民可以呈现什么肽 美国人和西班牙人的MHC等位基因，以及不同的抗原提呈如何在幽门螺杆菌中发挥作用 诱导炎症和胃癌的发生。我们的总体目标是定义幽门螺杆菌蛋白 在体外，美洲原住民和西班牙裔MHC等位基因普遍存在的表位空间，以及 这与普通高加索人MHC等位基因呈现的表位形成了对比。我们的假设是 常见的美洲原住民和西班牙裔MHC II类等位基因存在独特的幽门螺杆菌多肽 与更大的高加索人口相比。具体地说，我们的目标是SA1：执行全基因组测序 从美洲原住民分离的幽门螺杆菌菌株并从预测的序列中生成PepSeq表位文库 新的和当前基因组数据中的编码区，以及SA2：使用以下方法进行MHC-PepSeq结合研究 常见的美洲原住民和西班牙裔，以及普遍存在的美国MHC II类等位基因。我们希望 通过实验室和合成化学更好地了解常见的MHC II类的联系 种族群体内的抗原及其与来自高危人群的幽门螺杆菌的相互作用。如果成功，这将是 项目将在几个层面上产生影响：首先，它将向社区提供大量的 可能有助于幽门螺杆菌和幽门螺杆菌胃癌诊断的潜在的CD4+T细胞表位。第二，它 将确定少数群体独特的表位，这些表位可能会增加幽门螺杆菌感染的风险 胃癌。对于那些疾病风险较高的人，治疗干预是可能的。

Helicobacter pylori (H. pylori) is a bacterial infection which can be eradicated from the human body by most antibiotics, though, resistance is on the rise. The pathogen seems to play a role in healthy human digestion, as a component of the microbiome, but is also associated with development of ulcers, stomach cancer and stomach lymphomas. It is known that H. pylori-induced immune inflammation elevates the risk for gastritis and gastric cancer. In the United States (US), prevalence varies by geographic location, ethnic background, socioeconomic status, and age. For example, Navajo Nation members and Hispanics have disproportionately high rates of stomach cancer compared to Caucasians. While stomach cancer is associated with H. pylori infection, why certain populations are at increased risk at developing gastric cancer are not completely understood. Published studies suggest a role for H. pylori variation, human MHC types, and T cell response for inflammation and gastritis. However, the investigation into H. pylori variation and how human MHC present different peptides to the immune system have not been investigated at large scale. This proposal seeks to investigate this infectious-chronic disease interface by examining H. pylori genetic variation among Native Americans living in Northern Arizona and Hispanics, what peptides can be presented by common Native American and Hispanic MHC alleles, and how differential antigen presentation could play a role in H. pylori induced inflammation and gastric cancer development. Our overall goals are to define the H. pylori protein epitope space that could be commonly presented by Native American and Hispanic MHC alleles in vitro, and to contrast this with epitopes that are presented by common Caucasians MHC alleles. Our hypothesis is that there are unique H. pylori peptides presented by common Native American and Hispanic MHC class II alleles compared to the larger Caucasian population. Specifically, we aim to SA1: Perform whole genome sequencing of H. pylori strains isolated from Native Americans and generate PepSeq epitope libraries from predicted coding regions in the new and current genomic data, and SA2: Perform MHC-PepSeq binding studies using common Native American and Hispanic, as well as, generally common USA MHC class II alleles. We expect to better understand, through laboratory and synthetic chemistry the association of common MHC class II antigens within an ethic group and their interaction with H. pylori from high-risk populations. If successful, this project will have an impact at several levels: First, it will make available to the community a large set of potential CD4+ T cell epitopes that could assist in H. pylori and H. pylori gastric cancer diagnostics. Second, it will identify unique epitopes to a minority population that could contribute to increased risk of H. pylori induced gastric cancer. Therapeutic intervention is possible for those at high disease risk.