Bayele Henry K, Brown K Neil
Division of Parasitology, National Institute for Medical Research, London, UK.
FEMS Immunol Med Microbiol. 2007 Aug;50(3):389-95. doi: 10.1111/j.1574-695X.2007.00269.x. Epub 2007 May 30.
The 235-kDa antigenic rhoptry protein Py235 of Plasmodium yoelii is encoded by a large, highly polymorphic gene family. Monoclonal antibodies to some of these antigens have been shown to attenuate the virulence of the lethal YM strain of the parasite, converting a potentially fatal YM infection to a fulminating one typical of the nonlethal 17X strain, by inducing a switch in target cell preference from mature red blood cells to reticulocytes. The reason for this is not known but would suggest that antigenic determinants of Py235 may be useful in or as subunit vaccines. To identify such determinants, we constructed an epitope expression library of one Py235 variant and screened the library with the antibodies. Thus, we mapped 5- and 12-amino acid epitopes to the C-terminus of the antigen. Both epitopes were more reactive with protective than with nonprotective monoclonal antibodies. This may explain the differential protection conferred by these antibodies upon their passive transfer into mice.
约氏疟原虫的235-kDa抗原性棒状体蛋白Py235由一个庞大的、高度多态的基因家族编码。针对其中一些抗原的单克隆抗体已被证明可减弱该寄生虫致死性YM株的毒力,通过诱导靶细胞偏好从成熟红细胞转向网织红细胞,将潜在致命的YM感染转变为非致命性17X株典型的暴发性感染。其原因尚不清楚,但这表明Py235的抗原决定簇可能对亚单位疫苗有用或可作为亚单位疫苗。为了鉴定此类决定簇,我们构建了一个Py235变体的表位表达文库,并用这些抗体对文库进行筛选。因此,我们将5个和12个氨基酸的表位定位到该抗原的C末端。这两个表位与保护性单克隆抗体的反应性均高于非保护性单克隆抗体。这可能解释了这些抗体在被动转移到小鼠体内后所赋予的不同保护作用。