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甲基胆蒽诱导的小鼠肉瘤表达出各自独特的与主要组织相容性复合体I类相关的肽段,这些肽段可被特定的CD8 + T细胞系识别。

Methylcholanthrene-induced mouse sarcomas express individually distinct major histocompatibility complex class I-associated peptides recognized by specific CD8+ T-cell lines.

作者信息

Kono K, Petersson M, Ciupitu A M, Wen T, Klein G, Kiessling R

机构信息

Microbiology and Tumor Biology Center, Karolinska Institute, Stockholm, Sweden.

出版信息

Cancer Res. 1995 Dec 1;55(23):5648-55.

PMID:7585649
Abstract

Mouse sarcomas induced by methylcholanthrene (MC) are immunologically distinct even if they are induced in the same strain of mice. T-cell lines were derived from mice immunized against a series of syngeneic MC sarcomas on B6 background, known to carry unique tumor-specific transplantation antigens. Tumor necrosis factor-alpha (TNF-alpha) release assays concurred with the in vivo rejection tests. The strongest response in the TNF-alpha release was always obtained with the corresponding tumor, with very limited cross-reactivity against five other MC tumors or two virally induced B6 lymphomas. The specific TNF-alpha release from the anti-MC tumor CTL lines was mainly mediated by CD8+ cells. T-cell lines from intact and CD4-/- mice gave a similarly specific pattern. In contrast, T-cell lines derived from CD8-/- mice cross-reacted with several other MC-induced tumors. Peptides eluted from MC sarcomas under mild acid conditions were fractionated by reverse-phase high performance liquid chromatography and tested for their ability to sensitize the processing- and presentation-defective mutant RMA-S line. Only one high performance liquid chromatographic fraction from each of the three different tumor-derived peptide eluates capacitated RMA-S to induce TNF-alpha release and sensitized the cell to the cytotoxic effect of the corresponding tumor-specific T-cell line. A different Kb-restricted peptide fraction was active for each of the three MC sarcomas tested, indicating that they all expressed individually distinct peptide epitopes.

摘要

即使是由甲基胆蒽(MC)诱导产生的小鼠肉瘤,即便在同一品系的小鼠中诱导产生,其在免疫方面也是不同的。T细胞系源自免疫过一系列同基因MC肉瘤的小鼠,这些肉瘤以B6为背景,已知携带独特的肿瘤特异性移植抗原。肿瘤坏死因子-α(TNF-α)释放试验与体内排斥试验结果一致。在TNF-α释放试验中,对相应肿瘤的反应总是最强的,对其他五种MC肿瘤或两种病毒诱导的B6淋巴瘤的交叉反应非常有限。抗MC肿瘤CTL系特异性TNF-α的释放主要由CD8⁺细胞介导。来自完整小鼠和CD4⁻/⁻小鼠的T细胞系呈现出相似的特异性模式。相比之下,来自CD8⁻/⁻小鼠的T细胞系与其他几种MC诱导的肿瘤发生交叉反应。在温和酸性条件下从MC肉瘤洗脱的肽通过反相高效液相色谱进行分离,并测试其使加工和呈递缺陷的突变体RMA-S系致敏的能力。来自三种不同肿瘤来源的肽洗脱液中的每一种只有一个高效液相色谱级分能使RMA-S诱导TNF-α释放,并使细胞对相应肿瘤特异性T细胞系的细胞毒性作用敏感。对于所测试的三种MC肉瘤中的每一种,不同的Kb限制性肽级分都是有活性的,这表明它们都各自表达不同的肽表位。

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