ANTIGENICITY OF PROTEINS MODIFIED BY ALCOHOL METABOLITES

已有研究表明，长期饮酒会导致 蛋白质的化学变化的发展。据信， 酒精脱氢酶将酒精代谢为乙醛(AA)和 多不饱和脂肪对丙二醛的脂质过氧化作用 导致蛋白质与这两种醛物种的加合。 事实上，AA和MDA已被证明以一种协同的方式对 形成一种独特的加合物(MAA)，已在体外发现以及 在活体实验中。这种MAA加合物已被证明可以诱导 对MAA表位(S)和载体的强抗体反应 蛋白质，不使用佐剂。 我们假设，在长期饮用酒精后，MAA修饰的 蛋白质还诱导对MAA表位的独特免疫反应 AS，到可溶性载体蛋白上的未修饰表位。的能力 MAA修饰的可溶性蛋白诱导和免疫反应的依赖性 关于抗原处理抗原呈递的独特特征，以及 T细胞免疫调节回路的机制。 这项研究项目的主要目标是定义和 MAA加合物的体液和细胞免疫反应特征 蛋白质。为了确定主要参与摄取的细胞类型， MAA修饰蛋白质的加工和呈递及评估 这些免疫机制是否在发育和/或 酒精性肝病的进展。我们建议解决这些影响 关于这些问题的长期酒精消费的使用情况如下 具体目标：1)表征如果MAA加成的蛋白质 无MAA佐剂的诱导和抗体(体液免疫)反应 可溶性蛋白上的表位；2)表征T细胞对MAA的反应 免疫后加成的可溶性蛋白；3)细胞测定 参与吸收、处理和呈现的类型 MAA加成蛋白。

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.