Cloning and expression of Trypanosoma cruzi ribosomal protein P0 and epitope analysis of anti-P0 autoantibodies in Chagas' disease patients.
Cloning and expression of Trypanosoma cruzi ribosomal protein P0 and epitope analysis of anti-P0 autoantibodies in Chagas' disease patients.
复制标题
克隆和表达Cruzi核糖体蛋白P0和抗P0自身抗体的表位分析。
DOI：
10.1084/jem.176.1.201
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发表时间：
1992-07-01
影响因子：
15.3
通讯作者：
REED, SG
中科院分区：
文献类型：
--
作者：
SKEIKY, YAW;BENSON, DR;PARSONS, M;ELKON, KB;REED, SG
查加斯病由细胞内原生动物寄生虫克氏锥虫引起，是流行地区心力衰竭的主要原因。T.与宿主大分子共享表位的Cruzi抗原与发病机制有关，认为其具有重要的自身免疫成分。我们在此报告的克隆和鉴定全长cDNA从T。cruzi表达文库，其编码与人38-kD核糖体磷蛋白HuP 0同源的蛋白TcP 0。霸王cruzi P0蛋白显示了在高等真核生物中进化保守的残基簇。这包括与高电荷COOH末端相邻的富含丙氨酸和甘氨酸的区域。这个“标志”结构域是高免疫原性真核P蛋白家族交叉反应性的基础。我们找到了T.克氏病毒感染的个体具有与宿主（自身）P蛋白以及与重组TcP 0反应的抗体。缺失6个羧基端氨基酸后，T. Cruzi感染血清与TcP 0。这类似于针对患有系统性红斑狼疮（SLE）的患者的子集描述的抗P自身抗体的特异性（Elkon，K.，E.邦法河Llovet，W. Danho，H. Weissbach和N.兄弟1988. Proc. Natl. Acad. Sci. USA. 85：5186）。这些结果表明T. Cruzi P蛋白可能与Chagas病中自身反应性抗体的产生有关，并且抗P自身抗体的潜在机制在Chagas病和SLE患者中可能相似。本研究首次明确报道了克隆全长T。在结构、功能和共有抗原性方面模拟特征性宿主同源物的cruzi抗原。
Chagas' disease, caused by the intracellular protozoan parasite Trypanosoma cruzi, is a major cause of heart failure in endemic areas. Antigenic mimicry by T. cruzi antigens sharing epitopes with host macromolecules has been implicated in the pathogenesis which is thought to have a significant autoimmune component. We report herein on the cloning and characterization of a full-length cDNA from a T. cruzi expression library encoding a protein, TcP0, that is homologous to the human 38-kD ribosomal phosphoprotein HuP0. The T. cruzi P0 protein shows a clustering of residues that are evolutionarily conserved in higher eukaryotes. This includes an alanine- and glycine-rich region adjacent to a highly charged COOH terminus. This "hallmark" domain is the basis of the crossreactivity of the highly immunogenic eukaryotic P protein family. We found that T. cruzi-infected individuals have antibodies reacting with host (self) P proteins, as well as with recombinant TcP0. Deletion of the six carboxy-terminal amino acids abolished the reactivity of the T. cruzi infection sera with TcP0. This is similar to the specificity of anti-P autoantibodies described for a subset of patients with systemic lupus erythematosus (SLE) (Elkon, K., E. Bonfa, R. Llovet, W. Danho, H. Weissbach, and N. Brot. 1988. Proc. Natl. Acad. Sci. USA. 85:5186). These results suggest that T. cruzi P proteins may contribute to the development of autoreactive antibodies in Chagas' disease, and that the underlying mechanisms of anti-P autoantibody may be similar in Chagas' and SLE patients. This study represents the first definitive report of the cloning of a full-length T. cruzi antigen that mimics a characterized host homologue in structure, function, and shared antigenicity.
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影响因子：
9.4
作者：
MESRI, EA;LEVITUS, G;LEVIN, MJ
通讯作者：
LEVIN, MJ
DOI：
10.1073/pnas.89.4.1239
发表时间：
1992-02-15
影响因子：
11.1
作者：
BURNS, JM;SHREFFLER, WG;REED, SG
通讯作者：
REED, SG
DOI：
10.1111/j.1432-1033.1985.tb08968.x
发表时间：
1985-01-01
期刊：
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子：
--
作者：
MAASSEN, JA;SCHOP, EN;MOLLER, W
通讯作者：
MOLLER, W
影响因子：
2.9
作者：
CHOMCZYNSKI, P;SACCHI, N
通讯作者：
SACCHI, N
DOI：
10.1073/pnas.83.19.7419
发表时间：
1986-10-01
影响因子：
11.1
作者：
ELKON, K;SKELLY, S;BROT, N
通讯作者：
BROT, N