A novel T-cell receptor mimic defines dendritic cells that present an immunodominant West Nile virus epitope in mice.
A novel T-cell receptor mimic defines dendritic cells that present an immunodominant West Nile virus epitope in mice.
复制标题
一种新型 T 细胞受体模拟物定义了在小鼠体内呈现免疫显性西尼罗病毒表位的树突状细胞。
DOI：
10.1002/eji.201444450
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发表时间：
2014
影响因子：
5.4
通讯作者：
Hansen,TedH
中科院分区：
文献类型：
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作者：
Kim,Sojung;Pinto,AmeliaK;Myers,NancyB;Hawkins,Oriana;Doll,Krysten;Kaabinejadian,Saghar;Netland,Jason;Bevan,MichaelJ;Weidanz,JonA;Hildebrand,WilliamH;Diamond,MichaelS;Hansen,TedH
我们使用新生成的T细胞受体模拟单克隆抗体（TCRm MAb），该抗体识别西尼罗病毒（WNV）NS 4 B蛋白的已知非自身免疫显性肽表位，以研究C57 BL/6小鼠中病毒感染后的表位呈递。以前的研究表明，不同长度的肽，无论是SSVWNATTAI（10聚体）或SSVWNATTA（9聚体）与I类MHC抗原H-2Db复合，在WNV感染后免疫显性。我们的数据证实，这两种肽在WNV感染后都呈现在细胞表面，并且CD 8 +T细胞可以类似地检测10-和9-mer长度的变体。这一结果与给定的T细胞受体（TCR）偏好与其同源I类MHC结合的单个肽长度的想法不同。在使用TCRm单克隆抗体进行的单独的WNV感染研究中，我们表明，在体内，10-mer呈现在未感染和感染的CD 8 α+ CD 11 c+树突状细胞的表面上，这表明使用了直接和交叉呈现途径。相比之下，CD 11b + CD 11 c −细胞仅在被感染时才与TCRm单克隆抗体结合。我们的研究表明，TCR对肽的识别不限于某些肽长度，并且TCRm MAb可用于剖析体内抗原呈递的细胞类型特异性机制。
We used a newly generated T‐cell receptor mimic monoclonal antibody (TCRm MAb) that recognizes a known nonself immunodominant peptide epitope from West Nile virus (WNV) NS4B protein to investigate epitope presentation after virus infection in C57BL/6 mice. Previous studies suggested that peptides of different length, either SSVWNATTAI (10‐mer) or SSVWNATTA (9‐mer) in complex with class I MHC antigen H‐2Db, were immunodominant after WNV infection. Our data establish that both peptides are presented on the cell surface after WNV infection and that CD8+T cells can detect 10‐ and 9‐mer length variants similarly. This result varies from the idea that a given T‐cell receptor (TCR) prefers a single peptide length bound to its cognate class I MHC. In separate WNV infection studies with the TCRm MAb, we show that in vivo the 10‐mer was presented on the surface of uninfected and infected CD8α+CD11c+dendritic cells, which suggests the use of direct and cross‐presentation pathways. In contrast, CD11b+CD11c−cells bound the TCRm MAb only when they were infected. Our study demonstrates that TCR recognition of peptides is not limited to certain peptide lengths and that TCRm MAbs can be used to dissect the cell‐type specific mechanisms of antigen presentation in vivo.