IMMUNOBIOLOGY OF CAMPYLOBACTER JEJUNI

霍乱和沙门氏菌感染的致病机制研究 表明细菌鞭毛可能比仅仅 作为运动结构的。鞭毛状弯曲杆菌 鞭毛细丝的主要蛋白质，是主要的免疫显性 空肠弯曲菌在患者体内的蛋白表达 肠炎。鞭毛弯曲菌蛋白在致病中的作用 然而，最近的研究表明，弯曲杆菌感染的原因尚不清楚。 提示鞭毛蛋白可能含有一种粘附素，可以发挥 在与肠粘膜的相互作用中发挥作用。 流行病学和有限的志愿者挑战研究表明 感染后有免疫力，提示某些成分 空肠弯曲菌，也许还有鞭毛蛋白，可能对 免疫保护。 这项提案的具体目标是从生物化学和 免疫学上弯曲杆菌的某些抗原表位 鞭毛蛋白和对抗体的生物学性质进行表征 这些决定因素。我们将研究抗原性的结构 表位的化学和酶降解及免疫印迹 分析。我们将测定其组成、氨基酸序列 (S)，以及这些表位在化学和酶作用下的不稳定性 确定最低结构要求的方法 抗原性。我们将用固体合成这些表位- 阶段肽合成以进一步表征这些表位和 用于表征人类抗体反应。这个 通过制备标记物研究鞭毛蛋白表位的功能 合成肽和评估这些表位作为 粘附素。最后，我们将评估其生物学意义。 针对这些表位的人抗体(即固定化 活性、杀菌、粘附性抑制) 通过使用免疫吸附色谱柱获得特异性抗体 用合成多肽制备的。这些信息应该会导致 鞭毛蛋白在感染过程中作用的初步认识 并可能提出免疫保护的策略。

Studies on the pathogenesis of cholera and salmonella infections suggest that bacterial flagella may be more important than just serving as structures of motility. Campylobacter flagellin, the major protein of the flagella filament, is the major immunodominant protein of Campylobacter jejuni in patients will campylobacter enteritis. The role of campylobacter flagellin in the pathogenesis of campylobacter infection is unclear, however, recent studies suggest that the flagellin may possess an adhesin that could play a role in the interaction with the intestinal mucosa. Epidemiologic and limited volunteer challenge studies show that there is immunity after infection suggesting that some component of C. jejuni, and perhaps flagellin, may be useful for immunoprotection. The specific goals of this proposal are to define biochemically and immunologically some of the antigenic epitopes of campylobacter flagellin and to characterize biologically the nature of antibodies to these determinants. We will study the structure of antigenic epitopes by chemical and enzymatic degradation and immunoblot analysis. We will determine the composition, amino acid sequence (s), and lability of these epitopes by chemical and enzymatic methods to determine the minimal structural requirements for antigenic activity. We will synthesize these epitopes using solid- phase peptide synthesis to further characterize these epitopes and for use in characterizing the human antibody response. The function of flagellin epitopes will be studied by preparing labeled synthetic peptides and assessing the role of these epitopes as adhesins. Finally, we will assess the biological significance of human antibodies directed against these epitopes (i.e. immobilizing activity, bactericidal, inhibition of adherence) by isolating specific antibody through the use of immunoabsorbent columns prepared with synthetic peptides. This information should lead to a tetter understanding of the role of flagellin during infection and may suggest strategies for immunoprotection.