Design and use of conditional MHC class I ligands

Design and use of conditional MHC class I ligands
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DOI:
10.1038/nm1360
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发表时间:
2006-02-01
期刊:
影响因子:
82.9
通讯作者:
Schumacher, TNM
Schumacher, TNM
中科院分区:
医学1区
文献类型:
--
作者:
Toebes, M;Coccoris, M;Schumacher, TNM

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主要组织相容性复合体(MHC)I类分子在生物合成期间与多种肽配体缔合,并将这些配体呈递到细胞表面上以供细胞毒性T细胞识别。我们已经设计了条件性MHC配体,其与MHC分子形成稳定的复合物,但通过暴露于限定的光刺激而根据命令降解。以这种方式产生的“空MHC分子”可以负载肽配体阵列以确定MHC结合特性并以高通量方式监测抗原特异性T细胞应答。我们通过鉴定H5 N1流感病毒A/Vietnam/1194/04基因组内的细胞毒性T细胞表位来证明这种方法的价值。
Major histocompatibility complex (MHC) class I molecules associate with a variety of peptide ligands during biosynthesis and present these ligands on the cell surface for recognition by cytotoxic T cells. We have designed conditional MHC ligands that form stable complexes with MHC molecules but degrade on command, by exposure to a defined photostimulus. 'Empty MHC molecules' generated in this manner can be loaded with arrays of peptide ligands to determine MHC binding properties and to monitor antigen-specific T-cell responses in a high-throughput manner. We document the value of this approach by identifying cytotoxic T-cell epitopes within the H5N1 influenza A/Vietnam/1194/04 genome.