Quijada L, Requena J M, Soto M, Alonso C
Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Universidad Autónoma de Madrid, Spain.
Parasitology. 1996 Mar;112 ( Pt 3):277-84. doi: 10.1017/s0031182000065793.
A Leishmania infantum cDNA library was screened with sera from dogs with viscero-cutaneous leishmaniasis. Sequence analysis of a positive clone isolated from the library revealed that it coded for the carboxyl-terminal region of a member of the 70-kDa heat-shock protein family. The full-length sequence of the L. infantum hsp70 gene was determined after isolation of genomic clones. This protein shows a high degree of sequence conservation with the homologous protein from other organisms. To test its antigenicity a recombinant Hsp70 protein fused to the maltose-binding protein was produced in Escherichia coli using the expression vector pMAL-cRI. By FAST-ELISA assays it was observed that while the complete recombinant protein was recognized by 100% of the sera, the 20 carboxyl-terminal amino acids of the protein were only recognized by 30% of those sera. Thus, although a B-cell epitope must be present within the carboxyl terminal end of the protein other antigenic determinant(s) must reside out of this region. The analysis of the cross-reactivity with mouse Hsp70 by Western blotting strongly suggests that the anti-Hsp70 antibodies generated by infection with L. infantum are directed at specific determinants of the L. infantum Hsp70. Thus, our results indicate that anti-Hsp70 autoantibodies are not induced during Leishmania infection.
用来自患有内脏皮肤利什曼病的犬的血清筛选婴儿利什曼原虫cDNA文库。对从文库中分离出的一个阳性克隆进行序列分析,结果显示它编码70 kDa热休克蛋白家族成员的羧基末端区域。分离基因组克隆后确定了婴儿利什曼原虫hsp70基因的全长序列。该蛋白与其他生物体的同源蛋白表现出高度的序列保守性。为了测试其抗原性,使用表达载体pMAL-cRI在大肠杆菌中产生了与麦芽糖结合蛋白融合的重组Hsp70蛋白。通过快速酶联免疫吸附测定法观察到,虽然100%的血清能识别完整的重组蛋白,但该蛋白的20个羧基末端氨基酸仅被30%的血清识别。因此,虽然该蛋白的羧基末端必定存在一个B细胞表位,但其他抗原决定簇必定位于该区域之外。通过蛋白质印迹法分析与小鼠Hsp70的交叉反应性强烈表明,由婴儿利什曼原虫感染产生的抗Hsp70抗体针对的是婴儿利什曼原虫Hsp70的特定决定簇。因此,我们的结果表明,利什曼原虫感染期间不会诱导产生抗Hsp70自身抗体。