HLA Class I-T cell epitopes from trans-sialidase proteins reveal functionally distinct subsets of CD8+ T cells in chronic Chagas disease.
HLA Class I-T cell epitopes from trans-sialidase proteins reveal functionally distinct subsets of CD8+ T cells in chronic Chagas disease.
复制标题
来自跨硅酸盐酶蛋白的HLA I-T类细胞表位在慢性chagas病中揭示了CD8+ T细胞的功能不同的子集。
DOI：
10.1371/journal.pntd.0000288
复制
发表时间：
2008
影响因子：
3.8
通讯作者：
Laucella SA
中科院分区：
文献类型：
--
作者：
Alvarez MG;Postan M;Weatherly DB;Albareda MC;Sidney J;Sette A;Olivera C;Armenti AH;Tarleton RL;Laucella SA
以前，我们鉴定了一组HLA-A020.1限制性的转唾液酸酶肽，作为HLA-A0201+慢性T细胞感染个体中CD 8 + T细胞应答的靶点。克鲁兹在此，我们报告了识别由相同的转唾液酸酶基因家族编码的肽，其结合代表6种最常见的I类HLA超型的等位基因。基于生物信息学预测和HLA超型考虑的组合，选择了预测与HLA A01、A02、A03、A24、B7和B44超型结合的总共1001个表位。测试了由多个转唾液酸酶基因编码的96个超型结合表位在慢性T细胞白血病受试者的外周血中刺激回忆性CD 8 + T细胞应答的能力。无论HLA单倍型如何，cruzi感染。抗原性的总体层次是明显的，其中A02超型肽在恰加斯病人群中最常被识别，其次是A03和A24超型表位。CD 8 + T细胞对混杂表位的反应显示，T. cruzi的功能性特征是T细胞仅分泌干扰素-γ作为主要模式，而分泌IL-2的单个或分泌IFN-γ/IL-2的双重T细胞的发生率非常低，表明慢性T细胞缺乏多功能细胞因子应答。克氏感染本研究确定了一组T. cruzi肽，应证明可用于监测慢性恰加斯病个体的免疫能力和感染及疾病状态的变化。目前，中美洲和南美洲有1 600万至2 000万人感染克氏锥虫，这是人类恰加斯病的病原体。感染的主要临床后果是心肌病，约30%的感染者在初次感染多年后出现心肌病。我们在查加斯病患者中的工作开始于评估T细胞，特别是CD 8 + T细胞，在长期感染克氏锥虫的个体中识别的抗原的范围和特异性。T. Cruzi是主要的表面和释放的蛋白质，它们是体液和细胞免疫应答的靶标。我们以前鉴定了一组转唾液酸酶肽，它们被非常低频率的慢性T。克鲁兹感染者基于生物信息学的预测，在此我们报告了新的转唾液酸酶表位的鉴定，这些表位被更高比例的T。克鲁兹感染者对这些肽特异性的T细胞的功能谱是具有免疫系统长期刺激的感染的特征，具有高水平的IFN-γ分泌T细胞和低水平的IL-2产生。这套T。cruzi肽应该被证明可用于监测慢性恰加斯病个体的免疫能力和感染和疾病状态的变化。
Previously, we identified a set of HLA-A020.1-restricted trans-sialidase peptides as targets of CD8+ T cell responses in HLA-A0201+ individuals chronically infected by T. cruzi. Herein, we report the identification of peptides encoded by the same trans-sialidase gene family that bind alleles representative of the 6 most common class I HLA-supertypes. Based on a combination of bioinformatic predictions and HLA-supertype considerations, a total of 1001 epitopes predicted to bind to HLA A01, A02, A03, A24, B7 and B44 supertypes was selected. Ninety-six supertype-binder epitopes encoded by multiple trans-sialidase genes were tested for the ability to stimulate a recall CD8+ T cell response in the peripheral blood from subjects with chronic T. cruzi infection regardless the HLA haplotype. An overall hierarchy of antigenicity was apparent, with the A02 supertype peptides being the most frequently recognized in the Chagas disease population followed by the A03 and the A24 supertype epitopes. CD8+ T cell responses to promiscuous epitopes revealed that the CD8+ T cell compartment specific for T. cruzi displays a functional profile with T cells secreting interferon-γ alone as the predominant pattern and very low prevalence of single IL-2-secreting or dual IFN-γ/IL-2 secreting T cells denoting a lack of polyfunctional cytokine responses in chronic T. cruzi infection. This study identifies a set of T. cruzi peptides that should prove useful for monitoring immune competence and changes in infection and disease status in individuals with chronic Chagas disease. At present, 16–20 million people in Central and South America are infected with Trypanosoma cruzi, the causative agent of Chagas disease in humans. The primary clinical consequence of the infection is a cardiomyopathy, which manifests in approximately 30% of infected individuals, many years after the initial infection. Our work in Chagas disease patients began as an effort to assess the range and specificity of antigens that were recognized by T cells, in particular CD8+ T cells, in individuals with long-term infections with Trypanosoma cruzi. Trans-sialidase proteins from T. cruzi are major surface and released proteins that are targets of humoral and cellular immune responses. We previously, identified a set of trans-sialidase peptides that were recognized by a very low frequency of chronically T. cruzi-infected subjects. Based on bioinformatic predictions, herein we report the identification of new trans-sialidase epitopes that are recognized by a higher proportion of T. cruzi-infected people. The functional profile of T cells specific for these peptides is characteristic of an infection with long term stimulation of the immune system, with high levels of IFN-γ-secreting T cells and low levels of IL-2 production. This set of T. cruzi peptides should prove useful for monitoring immune competence and changes in infection and disease status in individuals with chronic Chagas disease.
登录
查看更多内容
影响因子：
4.4
作者：
Harari, A;Vallelian, F;Pantaleo, G
通讯作者：
Pantaleo, G
DOI：
10.1073/pnas.89.4.1239
发表时间：
1992-02-15
影响因子：
11.1
作者：
BURNS, JM;SHREFFLER, WG;REED, SG
通讯作者：
REED, SG
影响因子：
20.3
作者：
Harari, A;Petitpierre, S;Pantaleo, G
通讯作者：
Pantaleo, G
影响因子：
5.4
作者：
Frahm, Nicole;Yusim, Karina;Brander, Christian
通讯作者：
Brander, Christian
影响因子：
4.4
作者：
Albareda, MC;Laucella, SA;Postan, M
通讯作者：
Postan, M