Skeiky Y A, Benson D R, Elwasila M, Badaro R, Burns J M, Reed S G
Infectious Disease Research Institute, Seattle, Washington 98109.
Infect Immun. 1994 May;62(5):1643-51. doi: 10.1128/iai.62.5.1643-1651.1994.
Patients with visceral leishmaniasis produce high levels of immunoglobulin, but the specificities of antibodies produced are not well characterized. In an effort to identify leishmania antigens that are specific to Leishmania species or are cross-reactive with other parasitic protozoa, we have cloned and characterized full-length genomic and cDNA clones encoding a Leishmania chagasi acidic ribosomal antigen, LcP0, recognized during human infections. The protein is homologous to the Trypanosoma cruzi and human ribosomal proteins TcP0 and HuP0, respectively. Unlike most higher eukaryotes, but similar to TcP0, LcP0 has a C-terminal heptapeptide sequence resembling those of the archaebacterial acidic (P-like) proteins. The highly charged C-terminal acidic domain of LcP0 contains a serine residue typically found in most eukaryotes but lacking in all T. cruzi P proteins we have characterized thus far. L. chagasi-infected individuals as well as those with T. cruzi infections have antibodies cross-reactive with recombinant LcP0 and TcP0 as well as HuP0. However, the properties of anti-P0 antibodies in T. cruzi and L. chagasi infection sera are quite different. Through the use of synthetic peptides, we showed that while T. cruzi infection anti-TcP0 antibodies are exclusively directed against the C-terminal domain of TcP0, L. chagasi infection sera contain antibodies reactive with epitopes other than the C-terminal sequence of LcP0. Thus, anti-LcP0 antibodies in L. chagasi infection sera represent the first characterized deviation from the restricted immunodominant C-terminal epitope involved in the generation of anti-P0 antibodies following infection or autoimmune diseases.
内脏利什曼病患者会产生高水平的免疫球蛋白，但所产生抗体的特异性尚未得到充分表征。为了鉴定利什曼原虫属特异性或与其他寄生原生动物具有交叉反应性的利什曼原虫抗原，我们克隆并表征了编码一种在人类感染期间被识别的恰加斯利什曼原虫酸性核糖体抗原LcP0的全长基因组和cDNA克隆。该蛋白分别与克氏锥虫和人类核糖体蛋白TcP0和HuP0同源。与大多数高等真核生物不同，但与TcP0相似，LcP0具有一个C端七肽序列，类似于古细菌酸性（P样）蛋白的序列。LcP0高度带电荷的C端酸性结构域含有一个丝氨酸残基，该残基在大多数真核生物中常见，但在我们迄今表征的所有克氏锥虫P蛋白中均不存在。感染恰加斯利什曼原虫的个体以及感染克氏锥虫的个体都有与重组LcP0、TcP0以及HuP0发生交叉反应的抗体。然而，克氏锥虫和恰加斯利什曼原虫感染血清中抗P0抗体的特性有很大不同。通过使用合成肽，我们发现，虽然克氏锥虫感染的抗TcP0抗体仅针对TcP0的C端结构域，但恰加斯利什曼原虫感染血清中含有与LcP0 C端序列以外的表位发生反应的抗体。因此，恰加斯利什曼原虫感染血清中的抗LcP0抗体代表了首次发现的与感染或自身免疫性疾病后抗P0抗体产生所涉及的受限免疫显性C端表位不同的特征。
