Antigen processing in vivo and the elicitation of primary CTL responses.

Antigen processing in vivo and the elicitation of primary CTL responses.
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体内抗原加工和初级 CTL 反应的引发。

DOI:
10.4049/jimmunol.154.9.4414
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发表时间:
1995
影响因子:
4.4
通讯作者:
J. Bennink
J. Bennink
中科院分区:
医学2区
文献类型:
--
作者:
N. Restifo;I. Bačík;K. Irvine;J. Yewdell;Barbra Jill McCabe;Robert W. Anderson;L. Eisenlohr;Steven A. Rosenberg;J. Bennink

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CD8+ T 淋巴细胞 (TCD8+) 在细胞免疫反应中发挥重要作用。 TCD8+ 识别与 8 至 10 个残基的肽复合的 MHC I 类分子,这些残基主要源自胞质蛋白。通常认为蛋白质在细胞质中断裂,并通过 MHC 编码的肽转运蛋白递送至内质网 (ER) 中新生的 I 类分子。为了探索体内 TCD8+ 诱导在多大程度上受到蛋白水解或肽转运至 ER 的限制,用含有编码抗原肽的小基因(绕过蛋白水解的需要)或这些具有 NH2 末端 ER 插入序列的肽(绕过蛋白水解和转运的要求)的重组牛痘病毒对小鼠进行免疫。此外,用编码快速降解的蛋白质片段的重组牛痘病毒对小鼠进行免疫。我们报告说,不同抗原诱导 TCD8+ 反应的局限性各不相同:对于某些抗原来说,全长蛋白与其他测试形式一样具有免疫原性;对于其他人来说,最大反应是由肽或针对内质网的肽诱导的。最重要的是,在所检查的每种情况下,针对 ER 的肽从未减弱,在某些情况下大大增强了 TCD8+ 免疫反应,并为设计用于治疗癌症和传染病的活病毒或裸 DNA 疫苗提供了重要的替代策略。
CD8+ T lymphocytes (TCD8+) play an important role in cellular immune responses. TCD8+ recognize MHC class I molecules complexed to peptides of 8 to 10 residues derived largely from cytosolic proteins. Proteins are generally thought to be fragmented in the cytoplasm and delivered to nascent class I molecules in the endoplasmic reticulum (ER) by a peptide transporter encoded by the MHC. To explore the extent to which TCD8+ induction in vivo is limited by proteolysis or peptide transport into the ER, mice were immunized with recombinant vaccinia viruses containing mini-genes encoding antigenic peptides (bypassing the need for proteolysis), or these peptides with a NH2-terminal ER insertion sequence (bypassing the requirements for both proteolysis and transport). Additionally, mice were immunized with recombinant vaccinia viruses encoding rapidly degraded fragments of proteins. We report that limitations in induction of TCD8+ responses vary among Ags: for some, full length proteins are as immunogenic as other forms tested; for others, maximal responses are induced by peptides or by peptides targeted to the ER. Most importantly, in every circumstance examined, targeting peptides to the ER never diminished, and in some cases greatly enhanced, the TCD8+ immune response and provide an important alternative strategy in the design of live viral or naked DNA vaccines for the treatment of cancer and infectious diseases.
DOI: 10.4049/jimmunol.126.5.1814
发表时间: 1981-05
影响因子: 4.4
作者:
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DOI: --
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影响因子: --
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天然猿病毒 40 肿瘤抗原以及对应于 H-2Db 限制性表位的合成肽中的点突变对细胞毒性 T 淋巴细胞克隆的抗原呈递和识别的影响。
DOI: --
发表时间: 1992
期刊: Journal of immunology (Baltimore, Md. : 1950)
影响因子: --
作者:
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