Skeiky Y A, Benson D R, Guderian J A, Sleath P R, Parsons M, Reed S G
Seattle Biomedical Research Institute, WA 98109.
J Immunol. 1993 Nov 15;151(10):5504-15.
We have cloned and characterized cDNA molecules that encode members of the acidic ribosomal protein family (TcP proteins) from the protozoan parasite Trypanosoma cruzi. These proteins have been shown to be antigenic in individuals with T. cruzi infection. Unlike other known eukaryotic cells, T. cruzi possesses at least four types of P protein genes TcP0, TcP1, TcP2a, and TcP2b, each of which is present in multiple copies in the genome. These genes are present on at least three different chromosomes. Although the abundance of TcP0, TcP2a, and TcP2b transcripts do not appear to vary among the parasite life-cycle stages, TcP1 is predominantly expressed in the epimastigote (insect) stage. TcP0 has a C-terminal heptapeptide sequence that is similar to those of archaebacterial acidic (P-like) proteins, but the TcP1/P2 proteins terminate with a shared sequence characteristic of the P proteins of higher eukaryotes. The serine residues or other potential phosphorylation sites typically found within the highly charged C-terminal acidic domain are absent in T. cruzi P proteins. Using synthetic peptides, we demonstrated that approximately 80% of T. cruzi-infected individuals produce two distinct but cross-reactive anti-P antibody specificities directed against the C-termini of TcP0 and TcP1/P2. We also expressed the full length (non-fusion) recombinant human P0 and demonstrated that the T. cruzi anti-P antibodies cross-react with the C-terminal residues of human P-proteins. Conversely, human anti-P protein antibodies in sera from patients with SLE cross-react with the C-terminal epitope of T. cruzi TcP1/P2 proteins. The cross-reactivity of anti-TcP antibodies with human P proteins suggests that, through antigenic conservation, TcP proteins may contribute to the development of autoreactive antibodies in Chagas' disease patients.
我们已经克隆并鉴定了编码原生动物寄生虫克氏锥虫酸性核糖体蛋白家族（TcP蛋白）成员的cDNA分子。这些蛋白已被证明在克氏锥虫感染个体中具有抗原性。与其他已知的真核细胞不同，克氏锥虫拥有至少四种类型的P蛋白基因TcP0、TcP1、TcP2a和TcP2b，每种基因在基因组中都有多个拷贝。这些基因存在于至少三条不同的染色体上。尽管TcP0、TcP2a和TcP2b转录本的丰度在寄生虫生命周期各阶段似乎没有变化，但TcP1主要在无鞭毛体（昆虫）阶段表达。TcP0具有一个C末端七肽序列，与古细菌酸性（P样）蛋白的序列相似，但TcP1/P2蛋白以高等真核生物P蛋白共有的序列特征终止。克氏锥虫P蛋白中不存在通常在高度带电的C末端酸性结构域中发现的丝氨酸残基或其他潜在磷酸化位点。使用合成肽，我们证明约80%的克氏锥虫感染个体产生两种不同但交叉反应的抗P抗体特异性，分别针对TcP0和TcP1/P2的C末端。我们还表达了全长（非融合）重组人P0，并证明克氏锥虫抗P抗体与人P蛋白的C末端残基交叉反应。相反，系统性红斑狼疮患者血清中的人抗P蛋白抗体与克氏锥虫TcP1/P2蛋白的C末端表位交叉反应。抗TcP抗体与人P蛋白的交叉反应表明，通过抗原保守性，TcP蛋白可能在恰加斯病患者自身反应性抗体的产生中起作用。
