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首页> 美国卫生研究院文献>Proceedings of the National Academy of Sciences of the United States of America >Preprocalcitonin signal peptide generates a cytotoxic T lymphocyte-defined tumor epitope processed by a proteasome-independent pathway
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Preprocalcitonin signal peptide generates a cytotoxic T lymphocyte-defined tumor epitope processed by a proteasome-independent pathway

机译：降钙素原前信号肽产生通过蛋白酶体非依赖性途径加工的细胞毒性T淋巴细胞定义的肿瘤表位

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摘要

We identified an antigen recognized on a human non-small-cell lung carcinoma by a cytotoxic T lymphocyte clone derived from autologous tumor-infiltrating lymphocytes. The antigenic peptide is presented by HLA-A2 and is encoded by the CALCA gene, which codes for calcitonin and for the α-calcitonin gene-related peptide. The peptide is derived from the carboxy-terminal region of the preprocalcitonin signal peptide and is processed independently of proteasomes and the transporter associated with antigen processing. Processing occurs within the endoplasmic reticulum of all tumoral and normal cells tested, including dendritic cells, and it involves signal peptidase and the aspartic protease, signal peptide peptidase. The CALCA gene is overexpressed in medullary thyroid carcinomas and in several lung carcinomas compared with normal tissues, leading to recognition by the T cell clone. This new epitope is, therefore, a promising candidate for cancer immunotherapy.
机译：我们鉴定了人类非小细胞肺癌上的一种抗原，这种抗原是由自体肿瘤浸润淋巴细胞产生的细胞毒性T淋巴细胞克隆识别的。抗原肽由HLA-A2呈递，并由CALCA基因编码，CALCA基因编码降钙素和与α降钙素基因相关的肽。该肽衍生自降钙素原前信号肽的羧基末端区域，并且独立于蛋白酶体和与抗原加工有关的转运蛋白进行加工。加工发生在所有测试的肿瘤细胞和正常细胞（包括树突状细胞）的内质网内，并且涉及信号肽酶和天冬氨酸蛋白酶，信号肽肽酶。与正常组织相比，CALCA基因在甲状腺髓样癌和几种肺癌中过表达，从而导致T细胞克隆的识别。因此，这种新的表位是癌症免疫疗法的有希望的候选者。

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