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日本血吸虫22.6 kDa抗原作为人IgE反应主要靶点的鉴定:IgE结合表位与变应原肽的相似性

Identification of the Schistosoma japonicum 22.6-kDa antigen as a major target of the human IgE response: similarity of IgE-binding epitopes to allergen peptides.

作者信息

Santiago M L, Hafalla J C, Kurtis J D, Aligui G L, Wiest P M, Olveda R M, Olds G R, Dunne D W, Ramirez B L

机构信息

Schistosomiasis Study Group, Research Institute for Tropical Medicine, Alabang, Muntinlupa City, Philippines.

出版信息

Int Arch Allergy Immunol. 1998 Oct;117(2):94-104. doi: 10.1159/000023995.

Abstract

Human resistance to reinfection with Schistosoma mansoni and Schistosoma haematobium correlates with elevated IgE titers against worm antigens (soluble worm antigen preparation, SWAP). In S. mansoni infection, low levels of reinfection following chemotherapy are associated with the recognition of a cloned tegumental protein Sm22.6. Because of potential species-specific differences in resistance to schistosomes, we attempted to identify Schistosoma japonicum antigens recognized by human IgE. Following a survey of 176 infected individuals in Leyte, Philippines, we show that IgE antibodies from the majority of older, high-IgE/SWAP responders recognize antigens in the 22 (Sj22)-, 45-, 78- and 97-kDa range in SWAP. Limited IgE cross-reactivity between Sj22 and Sm22 was observed following a comparison of Filipino IgE responses to these antigens. The antigen was cloned from an adult S. japonicum lambda-ZAP cDNA library (Mindoro strain) by immunoscreening with pooled high-titer IgE antisera and a rabbit anti-Sj22 polyclonal antibody. The deduced amino acid sequence of the identified cDNA clone, MJ-1, showed significant homology to Sm22.6 (74%) and Sj22.6 (99%). Although the molecular sequence of Sj22.6 has already been reported, this is the first demonstration of its recognition by human IgE, thereby strengthening its potential as a vaccine candidate. Using an overlapping peptide approach, four IgE-binding epitopes were identified in Sj22.6, two of which exhibited similarities to known IgE-binding epitopes from codfish (Gad c 1) and beta-lactoglobulin-related allergens. These findings suggest that allergy and protective immunity to helminth infection may be linked by the structural similarities of epitopes recognized by human IgE.

摘要

人类对曼氏血吸虫和埃及血吸虫再感染的抵抗力与针对蠕虫抗原(可溶性蠕虫抗原制剂,SWAP)的IgE滴度升高相关。在曼氏血吸虫感染中,化疗后低水平的再感染与对克隆的体表蛋白Sm22.6的识别有关。由于对血吸虫的抵抗力可能存在物种特异性差异,我们试图鉴定人类IgE识别的日本血吸虫抗原。在对菲律宾莱特岛的176名感染者进行调查后,我们发现,大多数年龄较大、IgE/SWAP反应较高的应答者的IgE抗体识别SWAP中22 kDa(Sj22)、45 kDa、78 kDa和97 kDa范围内的抗原。比较菲律宾人对这些抗原的IgE反应后,观察到Sj22和Sm22之间有限的IgE交叉反应性。通过用合并的高滴度IgE抗血清和兔抗Sj22多克隆抗体进行免疫筛选,从日本血吸虫曼陀罗株的成人λ-ZAP cDNA文库中克隆出该抗原。鉴定出的cDNA克隆MJ-1的推导氨基酸序列与Sm22.6(74%)和Sj22.6(99%)具有显著同源性。尽管Sj22.6的分子序列已经报道,但这是首次证明其被人类IgE识别,从而增强了其作为疫苗候选物的潜力。使用重叠肽方法,在Sj22.6中鉴定出四个IgE结合表位,其中两个与已知的鳕鱼(Gad c 1)和β-乳球蛋白相关过敏原的IgE结合表位具有相似性。这些发现表明,对蠕虫感染的过敏和保护性免疫可能通过人类IgE识别的表位的结构相似性联系起来。

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