ANTIGENICITY OF PROTEINS MODIFIED BY ALCOHOL METABOLITES

酒精代谢物修饰的蛋白质的抗原性

• 批准号: 2682956
• 负责人: Monte S Willis
• 金额: $ 1.65万
• 依托单位: UNIVERSITY OF NEBRASKA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-04-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2682956
• 关键词: adduct; alcohol dehydrogenase; alcoholic beverage consumption; antigens; cell type; drug interactions; humoral immunity; intermolecular interaction; laboratory mouse; malonaldehyde; protein metabolism; protein transport; tissue /cell culture

It has been shown that long term alcohol ingestion can lead to the development of chemical changes to proteins. It is believed that metabolism of alcohol by alcohol dehydrogenase to acetaldehyde (AA) and lipid peroxidation of polyunsaturated fats to malondialdehyde (MDA) results in the adduction of proteins with both of these aldehyde species. In fact, AA and MDA have been shown to react in a synergistic manner to form a distinct adduct (MAA) that has been found in in vitro as well as in vivo experimentally. This MAA adduct has been shown to induce a strong antibody response to both the MAA epitope(s) and to the carrier protein without the use of adjuvants. We hypothesize that following chronic ethanol consumption MAA-modified proteins induce and unique immune response to the MAA-epitope, as well as, to nonmodified epitopes on soluble carrier proteins. The ability of MAA-modified soluble proteins to induce and immune response is dependent on unique features of antigen processing antigen presentation, and mechanisms of T-cell immunoregulatory circuits. The principal objective of this research project is to define and characterize the humoral and cellular immune responses to MAA-adducted proteins. To determine the cell types primarily involved in the uptake, processing and presentation of proteins modified by MAA and assess whether these immune mechanisms play a role in the development and/or progression of alcohol liver disease. We propose to address the effects of chronic ethanol consumption on these problems using the following specific aims: 1) Characterize the ability if MAA adducted proteins to induce and antibody (humoral immune) response without adjuvant to the MAA epitopes on soluble proteins; 2)Characterize the T cell response to MAA adducted soluble proteins following immunization; 3) Determine the cell types that are involved in the uptake, processing, and presentation of MAA-adducted proteins.

已经表明，长期饮酒会导致 蛋白质化学变化的发展。 相信 酒精对酒精脱氢酶的代谢为乙醛（AA）和 多不饱和脂肪脂于丙二醛（MDA）的脂质过氧化 导致将蛋白质与这两种醛物种合并。 实际上，AA和MDA已被证明以协同的方式对 在体外和 体内实验。 该MAA加合物已被证明会引起 对MAA表位和载体的强抗体反应强 蛋白质不使用佐剂。 我们假设慢性乙醇消耗后MAA修饰 蛋白质也会诱导MAA-蛋白质的独特免疫反应 AS，对可溶性载体蛋白的非修饰表位。能力 MAA修饰可溶性蛋白诱导和免疫反应取决于 关于抗原加工抗原表现的独特特征，以及 T细胞免疫调节电路的机制。 该研究项目的主要目标是定义和 表征了对MAA添加的体液和细胞免疫反应 蛋白质。 为了确定主要涉及摄取的细胞类型， 通过MAA修饰并评估的蛋白质的加工和表现 这些免疫机制是否在开发和/或 酒精肝病的进展。 我们建议解决效果 在这些问题上消耗慢性乙醇 具体目的：1）表征MAA加合蛋白的能力 诱导和抗体（体液免疫）反应，而无需辅助MAA 可溶性蛋白的表位； 2）表征T细胞对MAA的响应 免疫后加合的可溶性蛋白； 3）确定细胞 参与吸收，处理和表现的类型 MAA添加的蛋白质。