Both CD4+ and CD8+ T cell epitopes fused to heat shock cognate protein 70 (hsc70) can function to eradicate tumors
Both CD4+ and CD8+ T cell epitopes fused to heat shock cognate protein 70 (hsc70) can function to eradicate tumors
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DOI：
10.1111/j.1349-7006.2008.00788.x
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发表时间：
2008-05-01
期刊：
影响因子：
5.7
通讯作者：
Udono, Heiichiro
中科院分区：
文献类型：
--
作者：
Mizukami, Shusaku;Kajiwara, Chiaki;Udono, Heiichiro
用热休克蛋白（HSP）接种保护小鼠免受HSP从其分离的肿瘤的攻击。HSP疫苗的抗原性被认为是由HSP相关的内源性主要组织相容性复合物I类肽或其前体引起的。免疫效果可以在无佐剂的情况下实现，并且由CD 8（+）T细胞介导，表明HSP可以作为天然佐剂并在体内交叉致敏T细胞。我们先前设计了一种由融合到hsc 70羧基端的CD 8（+）T细胞表位组成的重组疫苗，并证明了用几微克的hsc 70-CTL表位融合蛋白接种后有效产生抗原特异性细胞毒性T淋巴细胞（CTL）。本研究旨在确定融合蛋白疫苗是否可以在体内控制肿瘤生长，以及与单独的CTL表位相比，将CD 4（+）T细胞表位同时融合到hsc 70-CTL表位的氨基末端是否是更有效的疫苗。将卵清蛋白（OVA）衍生的8聚体肽（OVA（257-264））和16聚体肽（OVA（265-280））分别用作CD 8（+）和CD 4（+）T细胞表位。用hsc 70-OVA（257-264）接种比肽加不完全弗氏佐剂组合更有效地产生肽特异性CTL，并抑制表达OVA的EL 4（E.G7）和B16黑素瘤肿瘤细胞的生长。将OVA（265-280）添加到hsc 70-OVA（257-264）的氨基末端（OVA（265-280）-hsc 70-OVA（257-264））增强了OVA（257 - 264）特异性CTL群体的产生，导致与hsc 70-OVA（257-264）相比更好地根除MO 5肺转移。我们的研究结果表明，融合CD 4（+）和CD 8（+）T细胞表位的hsc 70增强肿瘤免疫超过CD 8（+）T细胞表位单独的效果。
Vaccination with heat shock proteins (HSP) protects mice from challenge with the tumor from which the HSP were isolated. The antigenicity of HSP vaccination is thought to result from HSP-associated endogenous major histocompatibility complex class I peptides or their precursors. The vaccination effect can be achieved in an adjuvant-free manner and is mediated by CD8(+) T cells, indicating that HSP can act as a natural adjuvant and cross-prime T cells in vivo. We previously devised a recombinant vaccine composed of a CD8(+) T cell epitope fused to the carboxyl-terminus of hsc70 and demonstrated efficient generation of antigen-specific cytotoxic T lymphocyte (CTL) after vaccination with a few micrograms of the hsc70-CTL epitope fusion protein. The present study aimed to determine if the fusion protein vaccine could control tumor growth in vivo and whether simultaneous fusion of a CD4(+) T cell epitope to the amino terminus of the hsc70-CTL epitope would be a more potent vaccine compared to the CTL epitope alone. Ovalbumin (OVA)-derived 8 mer peptide, OVA(257-264), and 16mer peptide, OVA(265-280), were used as CD8(+) and CD4(+) T cell epitopes, respectively. Vaccination with hsc70-OVA(257-264) generated peptide specific CTL more effectively than a peptide plus incomplete Freund's adjuvant combination, and suppressed growth of OVA expressing EL4 (E.G7) and B16 melanoma tumor cells. Addition of OVA(265-280) to the amino-terminus of hsc70-OVA(257-264) (OVA(265-280)-hsc70-OVA(257-264)) enhanced the generation of the OVA(257-264)-specific CTL population, leading to better eradication of MO5 lung metastasis compared to hsc70-OVA(257-264). Our results suggest that fusion of both CD4(+) and CD8(+) T cell epitopes to hsc70 enhances tumor immunity beyond the effect of the CD8(+) T cell epitope alone.