A Novel Th Cell Epitope of Candida albicans Mediates Protection from Fungal Infection
A Novel Th Cell Epitope of Candida albicans Mediates Protection from Fungal Infection
复制标题
DOI：
10.4049/jimmunol.1200594
复制
发表时间：
2012-06-01
影响因子：
4.4
通讯作者：
LeibundGut-Landmann, Salome
中科院分区：
文献类型：
--
作者：
Baer, Eva;Gadiator, Andre;LeibundGut-Landmann, Salome
真菌病原体是机会性感染的常见原因。它们在健康个体中作为寄生虫生活，但当宿主的免疫状态改变时会引起疾病。T淋巴细胞在病原体控制中起关键作用。然而，确定抗真菌T细胞的活化和功能的特异性抗原在很大程度上仍然未知。通过使用免疫蛋白质组学的方法，我们已经确定了第一次，据我们所知，一个天然的T细胞表位从白色念珠菌。从感染的树突状细胞的MHC类H-结合配体的分离和测序揭示了一种肽，其被从感染的小鼠中分离的所有类特异性Th细胞的主要群体所识别。重要的是，人Th细胞也以HLA依赖性方式对肽的刺激作出反应，但不限于任何特定的HLA II类等位基因。用该肽免疫小鼠，产生了一群表位特异性Th细胞，它们不仅与C。白色念珠菌，但也与其他临床高度相关的念珠菌属物种，包括远亲光滑念珠菌。对不同念珠菌的反应程度与它们与念珠菌的系统发育关系有关。白色念珠菌最后，我们表明，新鉴定的肽作为一种有效的疫苗时，与佐剂诱导IL-17 A分泌肽特异性T细胞组合使用。免疫小鼠免受致命的念珠菌病。总之，这些结果揭示了一个新的免疫决定因素的主机响应念珠菌亚种。可以用来开发抗真菌疫苗和免疫疗法。免疫学杂志，2012，188：5636-5643。
Fungal pathogens are a frequent cause of opportunistic infections. They live as commensals in healthy individuals but can cause disease when the immune status of the host is altered. T lymphocytes play a critical role in pathogen control. However, specific Ags determining the activation and function of antifungal T cells remain largely unknown. By using an immunoproteomic approach, we have identified for the first time, to our knowledge, a natural T cell epitope from Candida albicans. Isolation and sequencing of MHC class H-bound ligands from infected dendritic cells revealed a peptide that was recognized by a major population of all Candida-specific Th cells isolated from infected mice. Importantly, human Th cells also responded to stimulation with the peptide in an HLA-dependent manner but without restriction to any particular HLA class II allele. Immunization of mice with the peptide resulted in a population of epitope-specific Th cells that reacted not only with C. albicans but also with other clinically highly relevant species of Candida including the distantly related Candida glabrata. The extent of the reaction to different Candida species correlated with their degree of phylogenetic relationship to C. albicans. Finally, we show that the newly identified peptide acts as an efficient vaccine when used in combination with an adjuvant inducing IL-17A secretion from peptide-specific T cells. Immunized mice were protected from fatal candidiasis. Together, these results uncover a new immune determinant of the host response against Candida ssp. that could be exploited for the development of antifungal vaccines and immunotherapies. The Journal of Immunology, 2012, 188: 5636-5643.