Within-host dynamics of antigenic variation
Within-host dynamics of antigenic variation
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DOI：
10.1016/j.meegid.2004.10.005
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发表时间：
2006-03-01
影响因子：
3.2
通讯作者：
Barbour, AG
中科院分区：
文献类型：
--
作者：
Frank, SA;Barbour, AG
一些寄生虫的基因组含有数十种替代且高度分化的表面抗原，其中只有一种在任何细胞中表达。单个细胞偶尔会改变其表面抗原的表达，从而使它们能够逃避免疫监视。这些转换似乎以部分随机的方式发生，产生了一组不同的抗原变体。尽管存在这种多样性，寄生虫血症还是以一系列暴发的形式发展，其中每次暴发都以相对较少的抗原类型为主。宿主特异性免疫最终清除了主要的抗原类型，并且新的爆发源于显然一直以低频率存在的抗原类型。这种不同抗原类型的顺序优势模式仍然无法解释。我们回顾了五个最著名的理论，这些理论主要是通过对原生动物锥虫和疟原虫以及细菌螺旋体疏螺旋体的研究而发展起来的。最有前途的理论依赖于某种机制的组合，以通过变体之间的转换矩阵创建有利的连接路径。有利的途径可能来自基因表达分子水平的偏向开关或免疫选择施加的前偏向。我们通过重新分析赫氏疏螺旋体变种之间的转变数据来说明连接途径的概念。 (c) 2006 Elsevier B.V. 保留所有权利。
Genomes of some parasites contain dozens of alternative and highly diverged surface antigens, of which only a single one is expressed in any cell. Individual cells occasionally change expression of their surface antigen, allowing them to escape immune surveillance. These switches appear to occur in a partly random way, creating a diverse set of antigenic variants. In spite of this diversity, the parasitemia develops as a series of outbreaks, in which each outbreak is dominated by relatively few antigenic types. Host-specific immunity eventually clears the dominant antigenic types, and a new Outbreak follows from antigenic types that have apparently been present all along at low frequency. This pattern of sequential dominance by different antigenic types remains unexplained. We review the five most prominent theories, which have developed mainly from studies of the protozoans Trypanosoma and Plasmodium, and the bacterial spirochete Borrelia. The most promising theories depend on some combination of mechanisms to create favored connectivity pathways through the matrix of transitions between variants. Favored pathways may arise from biased switches at the molecular level of gene expression or front biases imposed by immune selection. We illustrate the concept of connectivity pathways by reanalysis of data on transitions between variants from Borrelia hermsii. (c) 2006 Elsevier B.V. All rights reserved.