Immunological dominance of Trypanosoma cruzi tandem repeat proteins
Immunological dominance of Trypanosoma cruzi tandem repeat proteins
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DOI：
10.1128/iai.00604-08
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发表时间：
2008-09-01
影响因子：
3.1
通讯作者：
Reed, Steven G.
中科院分区：
文献类型：
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作者：
Goto, Yasuyuki;Carter, Darrick;Reed, Steven G.
在各种原生动物寄生虫中都发现了具有串联重复 (TR) 结构域的蛋白质，它们通常充当 B 细胞反应的靶标。然而，恰加斯病的病原体克氏锥虫内的重复程度尚未得到很好的研究。在这里，我们对克氏锥虫中发现的 TR 基因进行了系统调查，并与其他生物体进行了比较。尽管 TR 基因的特征因生物体而异，但具有大 TR 结构域的基因的存在对于所检查的锥虫科动物（包括克氏锥虫）来说是独特的。 T. cruzi TR 基因的序列分析揭示了它们的差异；它们不具有序列相似性或由信号序列或跨膜结构域的存在预测的有偏差的细胞位置等特征。相反，克氏锥虫TR蛋白似乎具有显着的抗原性。通过这种计算筛选，检测到了许多先前表征的克氏锥虫抗原，其中一些抗原含有一个大的 TR 结构域。对克氏锥虫基因组的进一步分析表明，该生物体中以前未表征的 TR 蛋白也可能是免疫显性的。总而言之，克氏锥虫富含具有免疫学意义的含有大TR结构域的蛋白质；值得进一步分析 TR 蛋白的特征，如重复序列的拷贝数和共有序列，以确定它们是否可能导致克氏锥虫菌株在诱导免疫反应、宿主易感性、疾病结果和致病性方面的生物变异性。
Proteins with tandem repeat (TR) domains have been found in various protozoan parasites, often acting as targets of B-cell responses. However, the extent of the repeats within Trypanosoma cruzi, the causative agent of Chagas' disease, has not been examined well. Here, we present a systematic survey of the TR genes found in T. cruzi, in comparison with other organisms. Although the characteristics of TR genes varied from organism to organism, the presence of genes having large TR domains was unique to the trypanosomatids examined, including T. cruzi. Sequence analyses of T. cruzi TR genes revealed their divergency; they do not share such characteristics as sequence similarity or biased cellular location predicted by the presence of a signal sequence or transmembrane domain(s). In contrast, T. cruzi TR proteins seemed to possess significant antigenicity. A number of previously characterized T. cruzi antigens were detected by this computational screening, and several of those antigens contained a large TR domain. Further analyses of the T. cruzi genome demonstrated that previously uncharacterized TR proteins in this organism may also be immunodominant. Taken together, T. cruzi is rich in large TR domain-containing proteins with immunological significance; it is worthwhile further analyzing such characteristics of TR proteins as the copy number and consensus sequence of the repeats to determine whether they might contribute to the biological variability of T. cruzi strains with regard to induced immunological responses, host susceptibility, disease outcomes, and pathogenicity.