A novel melanoma gene (MG50) encoding the interleukin 1 receptor antagonist and six epitopes recognized by human cytolytic T lymphocytes.
A novel melanoma gene (MG50) encoding the interleukin 1 receptor antagonist and six epitopes recognized by human cytolytic T lymphocytes.
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发表时间：
2000-11
期刊：
影响因子：
11.2
通讯作者：
Malcolm S. Mitchell;J. Kan‐Mitchell;Boris R. Minev;Carl Edman;Robert J. Deans
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作者：
Malcolm S. Mitchell;J. Kan‐Mitchell;Boris R. Minev;Carl Edman;Robert J. Deans
我们鉴定了一种新的 8.1 kb 人类黑色素瘤基因 MG50，该基因源自与鳞状肺癌细胞系 LU-1 的消减杂交。对包含开放阅读框的6.8 kb进行了测序，并推导了编码的1496个氨基酸的蛋白质的结构。使用 HLA-A2.1 转导的果蝇细胞作为抗原呈递细胞，我们鉴定了 HLA-A2.1 限制的 6 个可在体外诱导 CTL 的表位。 CTL 对含有 MG50 的黑色素瘤细胞的反应性表明表位是自然展示的。针对缺乏 HLA-A2.1 的黑色素瘤细胞系免疫的 CTL 的显着交叉反应性表明，至少有四个表位也在不同的 HLA I 类环境中被识别，最有可能是 HLA-A*6802。通过定量逆转录，在两种皮肤黑色素瘤细胞系之一、一种眼部黑色素瘤细胞系、四种转移性皮肤黑色素瘤中的两种、三种乳腺癌中的两种、两种结肠癌中的一种和一种卵巢癌中发现了 MG50 信息。在六种正常组织中，仅在正常皮肤标本中发现了 MG50，而先天性痣中则没有 MG50。 MG50很可能是白细胞介素1受体拮抗剂的基因，因为报道的后者的cDNA序列在3'区具有528个碱基的序列，是长连续碱基序列，并且编码176个与MG50相同的氨基酸。 MG50 是少数非分化抗原或突变蛋白的黑色素瘤相关抗原之一。由于其性质，它可能在其所在肿瘤的发病机制中发挥重要作用，并且是免疫原和免疫治疗的靶标。
We identified a novel 8.1-kb human melanoma gene, MG50, derived from subtractive hybridization with a squamous lung carcinoma cell line, LU-1. 6.8 kb containing an open reading frame were sequenced, and the structure of the encoded 1496 amino acid protein was deduced. With HLA-A2.1-transduced Drosophila cells as antigen-presenting cells, we identified six epitopes restricted by HLA-A2.1 that elicited CTLs in vitro. Reactivity of the CTLs to melanoma cells containing MG50 indicated that the epitopes were displayed naturally. Significant cross-reactivity of CTLs immunized against a melanoma cell line that lacked HLA-A2.1 indicated that at least four of the epitopes were also recognized in a different HLA class I context, most likely HLA-A*6802. By quantitative reverse transcription, MG50 message was found in one of two skin melanoma cell lines, an ocular melanoma cell line, two of four metastatic skin melanomas, two of three mammary carcinomas, one of two colon carcinomas, and an ovarian carcinoma. Of six normal tissues, MG50 was found only in a specimen of normal skin and was absent from a congenital nevus. It is likely that MG50 is the gene for the interleukin 1 receptor antagonist because a reported sequence of cDNA from the latter had a sequence of 528 bases in the 3' region, a long contiguous base sequence, and 176 encoded amino acids identical with those of MG50. MG50 is one of the few melanoma-associated antigens that is not a differentiation antigen or a mutated protein. Because of its nature, it may prove to be important in the pathogenesis of the tumors in which it is found, as well as an immunogen and target for immunotherapy.