Induction of a cytotoxic T-cell response to HIV-1 proteins with short synthetic peptides and human compatible adjuvants
Induction of a cytotoxic T-cell response to HIV-1 proteins with short synthetic peptides and human compatible adjuvants
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DOI：
10.1016/s0264-410x(01)00179-7
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发表时间：
2001-07-20
期刊：
影响因子：
5.5
通讯作者：
Corradin, G
中科院分区：
文献类型：
--
作者：
Peter, K;Men, Y;Corradin, G
本研究的目的是使用短的合成肽诱导针对HIV蛋白中存在的多个CTL表位的强CTL应答。在体外结合试验中显示与HLA-A2.1分子稳定结合的四种HLA-A2.1限制性肽（RT 476-484，p17 77-85，gp 41 814-823，RT 956-964）在注射IFA或Montanide（（R））时能够在HLA-A2.1转基因小鼠中引发强烈的特异性免疫应答。使用生物可降解微球（MS）作为佐剂也成功地测试了所有的肽。当肽作为混合物注射时，与肽的单独注射相比，反应较弱，表明免疫显性（ID）的发生。我们目前正在研究是否可以通过联合注射具有不同释放模式的负载肽的MS来克服ID。总之，用合成短肽和人相容性佐剂诱导HLA-A2.1转基因小鼠对几种HIV蛋白的特异性CTL应答似乎是可行的。(C)2001爱思唯尔科技有限公司版权所有。
The goal of this study was the induction of a strong CTL response against multiple CTL epitopes present in HIV proteins using short synthetic peptides. Four HLA-A2.1 restricted peptides (RT 476-484, p17 77-85, gp41 814-823, RT 956-964) that showed stable binding to the HLA-A2.1 molecule in an in vitro binding assay were able to elicit a strong specific immune response in HLA-A2.1 transgenic mice when injected with IFA or Montanide((R)). The use of biodegradable microspheres (MS) as adjuvant was also successfully tested for all peptides. When the peptides were injected as a mixture the response was weaker as compared to individual injections of the peptides indicating the occurrence of immunodominance (ID). We are currently investigating whether ID can be overcome by a combined injection of peptide loaded MS with different release patterns. Taken together, it seems feasible to induce a specific CTL response in HLA-A2.1 transgenic mice against several HIV proteins using short synthetic peptides and human compatible adjuvants. (C) 2001 Elsevier Science Ltd. All rights reserved.