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首页> 外文期刊>Infection and immunity >Repertoire of HLA-DR1-Restricted CD4 T-Cell Responses to Capsular Caf1 Antigen of Yersinia pestis in Human Leukocyte Antigen Transgenic Mice
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Repertoire of HLA-DR1-Restricted CD4 T-Cell Responses to Capsular Caf1 Antigen of Yersinia pestis in Human Leukocyte Antigen Transgenic Mice

机译：人类白细胞抗原转基因小鼠中鼠疫耶尔森氏菌荚膜Caf1抗原的HLA-DR1限制CD4 T细胞反应库。

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摘要

Yersinia pestis is the causative agent of plague, a rapidly fatal infectious disease that has not been eradicated worldwide. The capsular Caf1 protein of Y. pestis is a protective antigen under development as a recombinant vaccine. However, little is known about the specificity of human T-cell responses for Caf1. We characterized CD4 T-cell epitopes of Caf1 in “humanized” HLA-DR1 transgenic mice lacking endogenous major histocompatibility complex class II molecules. Mice were immunized with Caf1 or each of a complete set of overlapping synthetic peptides, and CD4 T-cell immunity was measured with respect to proliferative and gamma interferon T-cell responses and recognition by a panel of T-cell hybridomas, as well as direct determination of binding affinities of Caf1 peptides to purified HLA-DR molecules. Although a number of DR1-restricted epitopes were identified following Caf1 immunization, the response was biased toward a single immunodominant epitope near the C terminus of Caf1. In addition, potential promiscuous epitopes, including the immunodominant epitope, were identified by their ability to bind multiple common HLA alleles, with implications for the generation of multivalent vaccines against plague for use in humans.
机译：鼠疫耶尔森菌是鼠疫的病原体，鼠疫是一种致命的传染病，尚未在世界范围内根除。 Y的荚膜Caf1蛋白。鼠疫是一种正在开发的重组疫苗保护性抗原。但是，关于人类T细胞应答对Caf1的特异性了解甚少。我们在缺乏内源性主要组织相容性复合体II类分子的“人源化” HLA-DR1转基因小鼠中表征了Caf1的CD4 T细胞表位。用Caf1或一套完整的重叠合成肽中的每一种免疫小鼠，并通过一系列T细胞杂交瘤以及直接T细胞杂交瘤测定增殖，γ干扰素T细胞应答和识别的CD4 T细胞免疫确定Caf1肽与纯化的HLA-DR分子的结合亲和力。尽管在Caf1免疫后发现了许多DR1限制性抗原决定簇，但应答偏向于Caf1 C末端附近的单个免疫优势抗原决定簇。另外，潜在的混杂表位，包括免疫显性表位，通过它们结合多个常见HLA等位基因的能力而被鉴定，这暗示了用于人类的鼠疫多价疫苗的产生。

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