Diez H, López M C, Del Carmen Thomas M, Guzmán F, Rosas F, Velazco V, González J M, Puerta C
Laboratorio de Parasitología Molecular, Pontificia Universidad Javeriana, Bogotá, Colombia.
Parasite Immunol. 2006 Mar;28(3):101-5. doi: 10.1111/j.1365-3024.2005.00815.x.
The cellular response mediated by MHC class I restricted CD8+ T cells has been shown to be crucial in the control of Chagas disease. The K1 peptide derived from T. cruzi KMP-11 protein has a high binding affinity to the HLA-A0201 molecule. Nevertheless, it is not known whether this peptide is processed and displayed as an MHC class I epitope during natural infection by T. cruzi. The aim of this study was to evaluate, by ELISPOT assay, the ability of K1 peptide to activate CD8+ T lymphocytes to produce IFN-gamma. Therefore, CD8+ T lymphocytes from 22 HLA-A0201+ individuals, 12 chronic chagasic patients and 10 uninfected controls, were analysed. The results revealed that two of the chagasic patients had IFN-gamma-secreting CD8+ T cells that were able to respond to K1 peptide with a relative frequency of 110 and 230 per million CD8+ T cells. In contrast, none of HLA-A0201+ uninfected controls responded to K1 peptide. Responses to HLA-A0201 restricted peptide from the influenza matrix protein were found in six chagasic patients and four uninfected controls with an average frequency of 175 and 111 cells per million CD8+ T cells, respectively. Moreover, a flow cytometric assay for degranulation showed that chagasic responders had K1-specific cytotoxic CD8+ T cells. It is shown here for the first time that the K1 peptide is efficiently processed, presented and recognized by CD8+ T lymphocytes during the natural course of Chagas disease.
由MHC I类限制的CD8 + T细胞介导的细胞反应已被证明在恰加斯病的控制中至关重要。源自克氏锥虫KMP - 11蛋白的K1肽与HLA - A0201分子具有高结合亲和力。然而，尚不清楚该肽在克氏锥虫自然感染期间是否作为MHC I类表位被加工和呈递。本研究的目的是通过ELISPOT试验评估K1肽激活CD8 + T淋巴细胞产生IFN - γ的能力。因此，分析了来自22名HLA - A0201 +个体、12名慢性恰加斯病患者和10名未感染对照的CD8 + T淋巴细胞。结果显示，两名恰加斯病患者具有分泌IFN - γ的CD8 + T细胞，它们能够对K1肽作出反应，相对频率为每百万CD8 + T细胞110和230个。相比之下，HLA - A0201 +未感染对照中没有一个对K1肽有反应。在六名恰加斯病患者和四名未感染对照中发现了对来自流感基质蛋白的HLA - A0201限制肽的反应，平均频率分别为每百万CD8 + T细胞175和111个细胞。此外，脱颗粒的流式细胞术检测表明，恰加斯病反应者具有K1特异性细胞毒性CD8 + T细胞。首次表明，在恰加斯病的自然病程中，K1肽被CD8 + T淋巴细胞有效加工、呈递和识别。
