Induction of cellular immunity by immunization with novel hybrid peptides complexed to heat shock protein 70.
Induction of cellular immunity by immunization with novel hybrid peptides complexed to heat shock protein 70.
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DOI：
10.1073/pnas.97.7.3485
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发表时间：
2000-03
影响因子：
11.1
通讯作者：
Yoichi Moroi;Mark Mayhew;Jiri Trcka;Mee H. Hoe;Yoshizumi Takechi;F. Hartl;James E. Rothman;Alan N. Houghton
中科院分区：
文献类型：
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作者：
Yoichi Moroi;Mark Mayhew;Jiri Trcka;Mee H. Hoe;Yoshizumi Takechi;F. Hartl;James E. Rothman;Alan N. Houghton
来源于组织和细胞的热休克蛋白70 （hsp70）可以引起细胞毒性T淋巴细胞（CTL）对与hsp70结合的肽的反应。然而，多肽对热休克蛋白的亲和力可能存在显著差异，这可能限制了通过热休克蛋白免疫诱导CTL的多肽库。构建了hsp70肽结合位点的高亲和力配体通过甘氨酸-丝氨酸-甘氨酸连接体连接到T细胞表位的杂交肽。混合肽与小鼠hsp70复合物的免疫可以有效地引发小鼠特异性CTL反应，并且比单独与hsp70结合的T细胞肽表位更有效。在体内用hsp70和杂交多肽免疫可导致表达抗原的肿瘤的排斥反应，其效果比用多肽表位加hsp70免疫更有效。CTL反应的诱导不依赖于CD4(+) T细胞，这表明免疫直接启动抗原呈递细胞，在没有T细胞帮助的情况下引发CD8（+）细胞毒性T细胞反应。肽/hsp70复合物和小鼠hsp70均能诱导培养的小鼠骨髓源性树突状细胞（DC）释放细胞因子，包括内毒素抗性C57BL/10Sc小鼠的DC。因此，hsp70/杂化肽复合物可以激活DC以释放细胞因子，提供潜在的辅助作用，可以绕过T细胞的帮助。
Heat shock proteins 70 (hsp70) derived from tissues and cells can elicit cytotoxic T lymphocyte (CTL) responses against peptides bound to hsp70. However, peptides can markedly differ in their affinity for hsp, and this potentially limits the repertoire of peptides available to induce CTL by the hsp immunization. Hybrid peptides consisting of a high-affinity ligand for the peptide-binding site of hsp70 joined to T cell epitopes by a glycine-serine-glycine linker were constructed. Immunization with hybrid peptides complexed to mouse hsp70 effectively primed specific CTL responses in mice and were more potent than T cell peptide epitopes alone with hsp70. In vivo immunization with hsp70 and hybrid peptides led to rejection of tumors expressing antigen with greater efficacy than immunization with peptide epitope plus hsp70. Induction of CTL responses occurred independently of CD4(+) T cells, suggesting that immunization directly primed antigen-presenting cells to elicit CD8(+) cytotoxic T cell responses without T cell help. Both peptide/hsp70 complexes and mouse hsp70 alone were able to induce cultures of mouse bone marrow-derived dendritic cells (DC) to release cytokines, including DC from endotoxin-resistant C57BL/10Sc mice. Thus, hsp70/hybrid peptide complexes can activate DC for cytokine release, providing a potential adjuvant effect that could bypass T cell help.