Phage display of peptide epitopes from HIV-1 elicits strong cytolytic responses
Phage display of peptide epitopes from HIV-1 elicits strong cytolytic responses
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DOI：
10.1038/78490
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发表时间：
2000-08-01
影响因子：
46.9
通讯作者：
Guardiola, J
中科院分区：
文献类型：
--
作者：
De Berardinis, P;Sartorius, R;Guardiola, J
虽然人们在评价重组蛋白和合成肽作为免疫原方面做了很多工作，但它们通常被证明不能诱导有效的细胞毒性T细胞(CTL)反应，丝状噬菌体FD能在其主要外壳蛋白pVIII的N-末端展示多个拷贝的外来肽，其中2700个拷贝组成病毒衣壳，这里我们证明了Fd病毒展示肽RT2(ILKEPVHGV)，对应于HIV-1逆转录酶(RTase)的309-317残基，能够在人类细胞系中启动针对该HIV-1表位的CTL反应。成功的启动还需要一个T辅助表位Pep23(KDSWTVNDIQKLVGK)，对应于HIV-1 RTase的249-263位残基，通过将其展示在相同或单独的噬菌体病毒粒子上来提供这一表位，从而激活抗原特异性的CD4(+)T细胞。同样，用展示rt2肽的噬菌体病毒粒子免疫的人类白细胞抗原A2转基因小鼠，也能产生有效的、特异的抗HIV-rt2 CTL反应。这种意想不到的能力，除了B细胞反应外，还能诱导指定的细胞溶解T细胞反应，对于进入I类主要组织相容性复合体(MHC)载药室和重组疫苗的开发具有重要意义。
Although much effort has been expended on evaluating recombinant proteins and synthetic peptides as immunogens, they have generally proved incapable of inducing an efficient cytotoxic T-cell (CTL) response, Filamentous bacteriophage fd can display multiple copies of foreign peptides in the N-terminal region of its major coat protein pVIII, 2,700 copies of which make up the virus capsid, Here we show that fd virions displaying peptide RT2 (ILKEPVHGV), corresponding to residues 309-317 of the reverse transcriptase (RTase) of HIV-1, are able to prime a CTL response specific for this HIV-1 epitope in human cell lines. Successful priming also requires a T-helper epitope, pep23 (KDSWTVNDIQKLVGK), corresponding to residues 249-263 of HIV-1 RTase, Supplying this by displaying it on either the same or a separate bacteriophage virion led to activation of antigen-specific CD4(+) T cells. Likewise, HLA-A2 transgenic mice immunized with bacteriophage virions displaying peptide RT2 were shown to mount an effective, specific anti-HIV-RT2 CTL response. This unexpected ability to elicit a designated cytolytic T-cell response, in addition to a B-cell response, has important implications for access to the class I major histocompatibility complex (MHC) loading compartment and the development of recombinant vaccines.