HSP70 peptide binding mutants separate antigen delivery from dendritic cell stimulation
HSP70 peptide binding mutants separate antigen delivery from dendritic cell stimulation
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DOI：
10.1016/s1074-7613(03)00357-1
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发表时间：
2004-01-01
期刊：
影响因子：
32.4
通讯作者：
Lehner, PJ
中科院分区：
文献类型：
--
作者：
MacAry, PA;Javid, B;Lehner, PJ
微生物热休克蛋白(HSPs)与免疫反应的先天臂和适应性臂的诱导有关。我们现在发现，负载多肽的分枝杆菌HSP70复合体冲击的人树突状细胞(DC)可以产生强大的抗原特异性细胞毒性淋巴细胞(CTL)反应，这依赖于HSP70刺激的钙信号级联。根据计算的分枝杆菌HSP70(K-D=14微米)的多肽结合亲和力，我们表明120 PM HSP70结合的多肽足以产生多肽特异性的CTL反应，其效率比单独多肽高出四个数量级。最小的136个氨基酸，分枝杆菌HSP70肽结合域可以产生CTL反应，而一个单一氨基酸突变体HSP70旨在阻止肽结合但保留刺激能力，使我们能够将抗原传递与DC免疫刺激分开。
Microbial heat shock proteins (HSPs) have been implicated in the induction of both the innate and adaptive arms of the immune response. We now show that human dendritic cells (DC) pulsed with peptide-loaded mycobacterial HSP70 complexes generate potent antigen-specific cytotoxic lymphocyte (CTL) responses, which are dependent on an HSP70-stimulated calcium signaling cascade. From the calculated peptide binding affinity of mycobacterial HSP70 (K-D = 14 muM) we show that 120 pM HSP70 bound peptide is sufficient to generate a peptide-specific CTL response that is up to four orders of magnitude more efficient than peptide alone. The minimal 136 amino acid, mycobacterial HSP70 peptide binding domain can generate CTL responses, and a single amino acid mutant HSP70 designed to prevent peptide binding but retain stimulatory capacity has allowed us to separate antigen delivery from DC immunostimulation.