HLA-restricted epitope identification and detection of functional T cell responses by using MHC-peptide and costimulatory microarrays
HLA-restricted epitope identification and detection of functional T cell responses by using MHC-peptide and costimulatory microarrays
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DOI：
10.1073/pnas.0407019102
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发表时间：
2005-03-08
影响因子：
11.1
通讯作者：
Stern, LJ
中科院分区：
文献类型：
--
作者：
Stone, JD;Demkowicz, WE;Stern, LJ
T细胞表位的鉴定是研究对感染性物质和自身抗原的免疫反应的重要但往往缓慢和困难的一步。我们报道了一种空间可寻址的技术，用于筛选大量的T细胞表位，用于特异性抗原识别和诱导的功能活性。该系统使用固定的、重组的MHC-肽复合体、共刺激分子和细胞因子捕获抗体的微阵列。阵列元件作为合成的抗原提呈细胞，特异性地诱导T细胞反应，包括黏附、细胞因子的分泌和表面标志物的调节。该方法可以方便地识别大量候选的相关T细胞表位，并同时确定相互作用的功能结果。使用这种方法，我们已经表征了人的CD4(+)和CD8(+)T细胞对牛痘、流感、HIV-1和Epstein-Barr病毒的激活。
identification of T cell epitopes is a vital but often slow and difficult step in studying the immune response to infectious agents and autoantigens. We report a spatially addressable technique for screening large numbers of T cell epitopes for both specific antigen recognition and functional activity induced. This system uses microarrays of immobilized, recombinant MHC-peptide complexes, costimulatory molecules, and cytokine-capture antibodies. The array elements act as synthetic antigen-presenting cells and specifically elicit T cell responses, including adhesion, secretion of cytokines, and modulation of surface markers. The method allows facile identification of pertinent T cell epitopes in a large number of candidates and simultaneous determination of the functional outcome of the interaction. Using this method, we have characterized the activation of human CD4(+) and CD8(+) T cells responding to vaccinia, influenza, HIV-1, and Epstein-Barr viruses.