MAJOR TRYPANOSOMA-CRUZI ANTIGENIC DETERMINANT IN CHAGAS HEART-DISEASE SHARES HOMOLOGY WITH THE SYSTEMIC LUPUS-ERYTHEMATOSUS RIBOSOMAL P-PROTEIN EPITOPE

MAJOR TRYPANOSOMA-CRUZI ANTIGENIC DETERMINANT IN CHAGAS HEART-DISEASE SHARES HOMOLOGY WITH THE SYSTEMIC LUPUS-ERYTHEMATOSUS RIBOSOMAL P-PROTEIN EPITOPE
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DOI:
10.1128/jcm.28.6.1219-1224.1990
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发表时间:
1990-06-01
影响因子:
9.4
通讯作者:
LEVIN, MJ
LEVIN, MJ
中科院分区:
医学2区
文献类型:
--
作者:
MESRI, EA;LEVITUS, G;LEVIN, MJ

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克氏锥虫11 cDNA克隆JL 5表达了一种重组蛋白,发现该蛋白主要与慢性查加斯心脏病血清反应。克隆的35个残基长的肽被鉴定为T. cruzi核糖体P蛋白。JL 5 13个羧基端残基与系统性红斑狼疮(SLE)核糖体P蛋白表位具有高度同源性。使用包含JL 5蛋白的13(R-13)、10(R-10)和7(R-7)羧基末端残基的合成肽,通过酶联免疫吸附测定研究Chagas病抗JL 5和SLE抗P抗体的特异性。R-13肽定义了JL 5重组蛋白的线性抗原决定簇。如JL 5所证明的,R-13定义了在慢性Chagas心脏病患者中显著增加的抗体特异性。仅SLE抗P阳性血清与JL 5和R-13反应。精细表位作图显示,Chagas病抗JL 5抗体和SLE抗P抗体在R-13肽内定义了相似的表位。SLE血清与JL 5的结合被R-13肽完全阻断,表明抗JL 5和抗P自身抗体之间共有的特异性仅限于R-13肽内的保守线性表位。在Chagas心脏病患者中高抗R-13抗体滴度的流行支持了假设在Chagas心脏病中存在自身免疫性疾病的假设。
A Trypanosoma cruzi .lambda.gt11 cDNA clone, JL5, expressed a recombinant protein which was found to react predominantly with chronic Chagas'' heart disease sera. The cloned 35-residue-long peptide was identified as the carboxyl-terminal portion of a T. cruzi ribosomal P protein. The JL5 13 carboxyl-terminal residues shared a high degree of homology with the systemic lupus erythematosus (SLE) ribosomal P protein epitope. Synthetic peptides comprising the 13 (R-13), 10 (R-10), and 7 (R-7) carboxyl-terminal residues of the JL5 protein were used to study, by enzyme-linked immunosorbent assay, the specificity of the Chagas'' disease anti-JL5 and SLE anti-P antibodies. The R-13 peptide defined a linear antigenic determinant of the JL5 recombinant protein. As was proved for JL5, R-13 defined antibody specificities which were significantly increased in chronic Chagas'' heart disease patients. Only SLE anti-P positive sera were found to react with JL5 and R-13. Fine epitope mapping showed that Chagas'' disease anti-JL5 and SLE anti-P antibodies define similar epitopes within the R-13 peptide. The binding of the SLE sera to JL5 was completely blocked by the R-13 peptide, indicating that the shared specificity between anti-JL5 and anti-P autoantibodies was exclusively limited to the conserved linear epitope(s) within the R-13 peptide. The prevalence of high anti-R-13 antibody titers in Chagas'' heart disease patients supports the hypothesis that postulates the existence of autoimmune disorders in Chagas'' heart disease.