两个抗原被自体溶细胞的T淋巴细胞对黑色素瘤的结果从一个必不可少的管家基因的点突变。
文章的细节
-
引用
复制到剪贴板 -
希阿里R, Foury F, De Plaen E, Baurain摩根富林明,Thonnard J, Coulie PG
两个抗原被自体溶细胞的T淋巴细胞对黑色素瘤的结果从一个必不可少的管家基因的点突变。
癌症研究》1999年11月15日,59 (22):5785 - 92。
- PubMed ID
-
10582700 (在PubMed]
- 文摘
-
我们追求分析自体抗原识别的细胞溶解的T淋巴细胞(ctl)对黑色素瘤细胞的病人LB33。这个病人享有异常有利的进化,这是与一个强大和可持续的抗肿瘤CTL反应有关。我们先前报道的分析两个黑素瘤细胞系,梅尔。一个和梅尔。B,它来自转移从病人在5年的距离。自体的细胞毒性t淋巴细胞克隆来自血液淋巴细胞识别抗原的不同HLA类我MEL.A分子。梅尔。B细胞抵制这些ctl细胞溶解,因为他们失去了大多数HLA分子的表达,这表明他们选择anti-MEL体内。CTL反应。梅尔·之一。抗原被证明的结果从一个点突变的肿瘤。在这里,我们报告的克隆基因编码两个梅尔。一个抗原。 This new gene, MUM-2, is expressed ubiquitously. In the melanoma cells of patient LB33, it contains a point mutation that changes one amino acid in the translated protein. Two different antigenic peptides, one presented to CTL by HLA-B44 molecules and another by HLA-C6 molecules, overlap and contain the mutated residue. Gene MUM-2 is homologous to an essential yeast gene, bet5, that was recently shown to be implicated in the vesicular transport of proteins from the endoplasmic reticulum to the Golgi. In a mutant yeast with a disrupted bet5 gene, both the wild-type and the mutated MUM-2 genes could complement for bet5 function. These results indicate that the antigenic mutation does not destroy the function of the protein, a function that is conserved in eukaryotic cells. The identification of these antigens suggests that point mutations could be the major cause of the strong immunogenicity of MEL.A cells.