Low H P, Santos M A, Wizel B, Tarleton R L
Department of Cellular Biology, University of Georgia, Athens 30602, USA.
J Immunol. 1998 Feb 15;160(4):1817-23.
Amastigotes of Trypanosoma cruzi express surface proteins that, when released into the host cell cytoplasm, are processed and presented on the surface of infected cells in the context of MHC class I molecules to be recognized by CD8+ CTL. To further understand the role of CTL in T. cruzi infection, we used the available MHC class I peptide binding motifs to identify potential CTL target epitopes in two recently described T. cruzi amastigote surface proteins, ASP-1 and ASP-2. The predicted amino acid sequences of ASP-1 and ASP-2 were screened for H-2b allele-specific class I peptide motifs, and four peptides (PA11, PA12, PA13, and PA14) and six peptides (PA5, PA6, PA7, PA8, PA9, and PA10) were synthesized from ASP-1 and ASP-2, respectively. The majority of the peptides bound to some degree to H-2b class I MHC molecules, and six of 10 of the peptides stimulated spleen cells from T. cruzi-infected mice to lyse target cells sensitized with the homologous peptides. Short term T cell lines specific for three of these peptides also lysed T. cruzi-infected target cells. These results demonstrate that ASP-1 and ASP-2 are targets of in vivo generated CTLs and that this CTL response induced by T. cruzi infection is parasite and peptide specific, MHC restricted, and CD8 dependent.
克氏锥虫无鞭毛体表达表面蛋白，这些蛋白释放到宿主细胞质后，会被加工处理，并在MHC I类分子的作用下呈递到被感染细胞表面，以供CD8 + CTL识别。为了进一步了解CTL在克氏锥虫感染中的作用，我们利用现有的MHC I类肽结合基序，在最近描述的两种克氏锥虫无鞭毛体表面蛋白ASP - 1和ASP - 2中鉴定潜在的CTL靶表位。对ASP - 1和ASP - 2的预测氨基酸序列进行H - 2b等位基因特异性I类肽基序筛选，分别从ASP - 1和ASP - 2合成了4种肽（PA11、PA12、PA13和PA14）和6种肽（PA5、PA6、PA7、PA8、PA9和PA10）。大多数肽在一定程度上与H - 2b I类MHC分子结合，10种肽中有6种刺激来自克氏锥虫感染小鼠的脾细胞裂解用同源肽致敏的靶细胞。针对其中3种肽的短期T细胞系也能裂解克氏锥虫感染的靶细胞。这些结果表明，ASP - 1和ASP - 2是体内产生的CTL的靶标，并且克氏锥虫感染诱导的这种CTL反应具有寄生虫和肽特异性、MHC限制性以及CD8依赖性。
