Garg N, Nunes M P, Tarleton R L
Department of Cellular Biology, University of Georgia, Athens 30602, USA.
J Immunol. 1997 Apr 1;158(7):3293-302.
Class I MHC-restricted T cell responses have been shown to be critical for the development of immune resistance to Trypanosoma cruzi in mice. However, to date, no antigenic targets of this anti-parasite response have been characterized. We have analyzed the characteristics of potential T. cruzi CTL target molecules by expression of the model CTL target molecule chicken OVA in different cellular compartments of T. cruzi. OVA (amino acids 139-385) was expressed as a secretory, cytoplasmic, transmembrane, or glycosylphosphatidylinositol-anchored protein in T. cruzi transfectants. Host cells infected with T. cruzi transfectants that secreted or released OVA, but not those producing cytoplasmic or transmembrane forms of OVA, could process and present OVA peptide via the class I MHC pathway, as indicated by the stimulation of OVA-specific CD8+ T cell hybridomas and the cytolysis of host cells infected with OVA-secreting parasites by OVA-specific CTLs. In addition, infection of mice with OVA-secreting parasites elicited the production of OVA-specific CTLs. These studies demonstrate the ability to target proteins to specific cellular compartments in T. cruzi using either trypanosomal or mammalian signal sequences. Furthermore, these results suggest that proteins secreted or released by T. cruzi in infected cells are a major source of peptides for MHC class I presentation and for the generation of parasite-specific CTL.
I类主要组织相容性复合体（MHC）限制的T细胞反应已被证明对小鼠抵抗克氏锥虫的免疫发展至关重要。然而，迄今为止，这种抗寄生虫反应的抗原靶点尚未得到鉴定。我们通过在克氏锥虫的不同细胞区室中表达模型CTL靶分子鸡卵清蛋白（OVA），分析了潜在的克氏锥虫CTL靶分子的特征。OVA（氨基酸139 - 385）在克氏锥虫转染体中表达为分泌型、胞质型、跨膜型或糖基磷脂酰肌醇锚定蛋白。感染分泌或释放OVA的克氏锥虫转染体的宿主细胞，而不是产生胞质或跨膜形式OVA的宿主细胞，能够通过I类MHC途径加工和呈递OVA肽，这通过OVA特异性CD8 + T细胞杂交瘤的刺激以及OVA特异性CTL对感染分泌OVA寄生虫的宿主细胞的细胞溶解来表明。此外，用分泌OVA的寄生虫感染小鼠会引发OVA特异性CTL的产生。这些研究证明了使用锥虫或哺乳动物信号序列将蛋白质靶向克氏锥虫特定细胞区室的能力。此外，这些结果表明，克氏锥虫在感染细胞中分泌或释放的蛋白质是MHC I类呈递肽和产生寄生虫特异性CTL的主要来源。
