Cross‐presentation of NY‐ESO‐1 cytotoxic T lymphocyte epitope fused to human heat shock cognate protein 70 by dendritic cells
Cross‐presentation of NY‐ESO‐1 cytotoxic T lymphocyte epitope fused to human heat shock cognate protein 70 by dendritic cells
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树突状细胞与人热休克同源蛋白 70 融合的 NY-ESO-1 细胞毒性 T 淋巴细胞表位的交叉呈递
DOI：
10.1111/j.1349-7006.2007.00654.x
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发表时间：
2007
期刊：
影响因子：
5.7
通讯作者：
T. Kanematsu
中科院分区：
文献类型：
--
作者：
S. Susumu;Y. Nagata;S. Ito;M. Matsuo;D. Valmori;K. Yui;H. Udono;T. Kanematsu
癌睾丸抗原NY‐ESO‐1已被认为是最有吸引力的癌症疫苗候选物之一。然而，蛋白质疫苗通常会遇到抗原向CD8+ T细胞呈递效率低下的问题，这可以通过与适当的佐剂结合来克服。热休克蛋白是一种天然佐剂，可激活抗原呈递细胞，将外源抗原导入经典的主要组织相容性复合体I类抗原加工途径（交叉呈递）。因此，我们将一个包含NY‐ESO‐1细胞毒性T淋巴细胞（CTL）表位157‐165 （ESO p157‐165）的迷你基因与人热休克同源蛋白70 （hsc70）基因融合，并在大肠杆菌中表达融合蛋白。通过使用人白细胞抗原- a *0201限制性NY - ESO - 1特异性CTL克隆，研究了单核细胞来源的树突状细胞（mo - DC）与融合蛋白的交叉呈递ESO p157 - 165。融合蛋白-脉冲mo - DC比游离NY - ESO - 1蛋白-脉冲mo - DC更有效地激活CTL克隆。此外，ESO p157‐165与hsc70和ESO p157‐165的融合蛋白（hsc70 - ESO p157‐165融合蛋白）之间的CTL活性大小相当。此外，融合蛋白诱导的CTL活化，而不是由表位引起的，可以通过mo - DC的多聚甲醛固定和蛋白酶体的特异性抑制剂lactacystin处理来抑制。最后，hsc70-ESO p157 - 165融合蛋白脉冲DC能够诱导抗原特异性T细胞反应。这些结果表明，hsc70-ESO p157‐165融合蛋白因此被认为是一种有希望的癌症疫苗候选蛋白。（癌症科学2008；99:107-112）
The cancer–testis antigen NY‐ESO‐1 has been implicated as one of the most attractive candidates for a cancer vaccine. However, a protein vaccine generally meets inefficient antigen presentation to CD8+ T cells, which could be overcome by combination with an appropriate adjuvant. Heat shock protein is a natural adjuvant and activates the antigen‐presenting cells to channel exogenous antigens into the classical major histocompatibility complex class I antigen‐processing pathway (cross‐presentation). Therefore, we genetically fused a minigene encompassing the NY‐ESO‐1 cytotoxic T lymphocyte (CTL) epitope 157‐165 (ESO p157‐165) to the human heat shock cognate protein 70 (hsc70) and expressed the resulting fusion proteins in Escherichia coli. By using a human leukocyte antigen‐A*0201‐restricted NY‐ESO‐1‐specific CTL clone, the cross‐presentation of ESO p157‐165 by monocyte‐derived dendritic cells (mo‐DC) pulsed with the fusion protein was evaluated. The fusion protein‐pulsed mo‐DC activates the CTL clone much more efficiently than the free NY‐ESO‐1 protein‐pulsed mo‐DC. Moreover, the magnitude of the CTL activity was comparable between ESO p157‐165 and the fusion protein of hsc70 and ESO p157‐165 (hsc70–ESO p157‐165 fusion protein). In addition, the CTL activation induced by the fusion protein, but not by the epitope, was inhibited by paraformaldehyde fixation of the mo‐DC and by treatment with lactacystin, a specific inhibitor for the proteasome. Finally, the hsc70–ESO p157‐165 fusion protein‐pulsed DC was able to induce an antigen‐specific T‐cell response. These results suggest that the hsc70–ESO p157‐165 fusion protein is therefore considered to be a promising candidate as a cancer vaccine. (Cancer Sci 2008; 99: 107–112)
影响因子：
32.4
作者：
Basu, S;Binder, RJ;Srivastava, PK
通讯作者：
Srivastava, PK
影响因子：
56.9
作者：
SUTO, R;SRIVASTAVA, PK
通讯作者：
SRIVASTAVA, PK