Wizel B, Nunes M, Tarleton R L
Department of Cellular Biology, University of Georgia, Athens 30602, USA.
J Immunol. 1997 Dec 15;159(12):6120-30.
CD8+ T lymphocytes play a critical role in immunity to Trypanosoma cruzi. However, the target molecules of this T cell subset have not been elucidated. In this work, we report the identification of an H-2Kb-restricted CTL epitope within two trypomastigote surface Ags encoded by members of the T. cruzi sialidase/trans-sialidase gene superfamily. Octapeptide VDYNFTIV sensitized target cells for lysis by CD8+ CTL generated from spleens of T. cruzi-infected mice. Peptide-specific CD8+ T cell lines were cytotoxic, secreted IFN-gamma and TNF-alpha, but low to undetectable levels of IL-4 and IL-5, and were able, upon adoptive transfer, to confer a high degree of protection against challenge infection. Finally, the protective determinant appears to be conserved among parasites from diverse geographic locations. This constitutes the first identified class I MHC-restricted epitope in T. cruzi and provides the basis for the search of additional targets to be considered in the development of vaccines against Chagas' disease.
CD8 + T淋巴细胞在抗克氏锥虫免疫中发挥关键作用。然而，该T细胞亚群的靶分子尚未阐明。在本研究中，我们报告了在克氏锥虫唾液酸酶/转唾液酸酶基因超家族成员编码的两种锥鞭毛体表面抗原内鉴定出一个H - 2Kb限制性CTL表位。八肽VDYNFTIV使靶细胞对来自克氏锥虫感染小鼠脾脏产生的CD8 + CTL介导的裂解敏感。肽特异性CD8 + T细胞系具有细胞毒性，分泌IFN - γ和TNF - α，但IL - 4和IL - 5水平低至无法检测，并且在过继转移后能够对攻击感染提供高度保护。最后，该保护性决定簇在来自不同地理位置的寄生虫中似乎是保守的。这是首次在克氏锥虫中鉴定出的I类MHC限制性表位，并为寻找在开发抗恰加斯病疫苗时要考虑的其他靶标提供了基础。
