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The SA85-1.1 Protein of the Trypanosoma cruzi trans-Sialidase Superfamily Is a Dominant T-Cell Antigen

机译:克氏锥虫反唾液酸酶超家族的SA85-1.1蛋白是主要的T细胞抗原。

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Trypanosoma cruzi currently infects 18 million people, and 30% of those infected develop a chronic inflammatory process that causes significant morbidity or mortality. The major histocompatibility complex class II (MHC-II)-restricted T-cell response is critical to the control of the infection and to the ensuing inflammatory pathology. The specific epitopes or major antigens of this response have not been identified. The parasite simultaneously expresses variant members of the trans-sialidase superfamily. To begin to analyze the MHC-II response to these variant proteins, the response to a single surface protein, SA85-1.1, was initiated. These studies have demonstrated that a biased gamma interferon (IFN-γ) response to the SA85-1.1 protein develops during T. cruzi infection. In addition, adoptive transfer of a CD4 clone that recognizes an SA85-1.1 epitope, named epitope 1, and immunization with a peptide encoding epitope 1 were protective and suggested that epitope 1 may be immunodominant. In this report IFN-γ intracellular staining demonstrated that splenocytes from acutely and chronically infected mice, incubated with SA85-1.1 protein or peptides that encode epitope 1, result in IFN-γ synthesis by 4 to 6% of the splenic CD4 cells. These data indicate that during T. cruzi infection epitope 1 is a major epitope and that 4 to 6% of the CD4 cells are stimulated by a single trans-sialidase superfamily epitope and suggest that a combination of trans-sialidase superfamily proteins combines to stimulate a majority of CD4 cells. These data suggest that during T. cruzi infection the CD4 response to thetrans-sialidase superfamily is critical to the protective response and to the ensuing chronic inflammatory pathology.
机译:克氏锥虫目前感染1800万人,其中30%的人发展为慢性炎症过程,导致明显的发病率或死亡率。主要的组织相容性复合物II类(MHC-II)限制性T细胞反应对于控制感染和随后的炎症病理至关重要。该反应的特定表位或主要抗原尚未鉴定。寄生虫同时表达反唾液酸酶超家族的变体成员。为了开始分析MHC-II对这些变异蛋白的反应,开始了对单一表面蛋白SA85-1.1的反应。这些研究表明,在克氏锥虫感染过程中对SA85-1.1蛋白产生了偏向性的γ干扰素(IFN-γ)反应。此外,识别SA85-1.1表位(称为表位1)的CD4克隆的过继转移和用编码表位1的肽免疫是保护性的,表明表位1可能具有免疫优势。在该报告中,IFN-γ细胞内染色表明,与SA85-1.1蛋白或编码表位1的肽孵育的急性和慢性感染小鼠的脾细胞导致脾脏CD4细胞中IFN-γ的合成达到4%至6%。这些数据表明,在克鲁维氏菌感染期间,表位1是主要表位,单个反唾液酸酶超家族表位可刺激4-6%的CD4细胞,这表明反唾液酸酶超家族蛋白的组合可刺激大多数CD4细胞。这些数据表明,在克氏锥虫感染期间,对反唾液酸酶超家族的CD4应答对于保护应答和随后的慢性炎症病理至关重要。

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