Alternative Variants of Human HYDIN Are Novel Cancer-Associated Antigens Recognized by Adaptive Immunity
Alternative Variants of Human HYDIN Are Novel Cancer-Associated Antigens Recognized by Adaptive Immunity
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DOI：
10.1158/2326-6066.cir-13-0079
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发表时间：
2013-09-01
影响因子：
10.1
通讯作者：
Gouttefangeas, Cecile
中科院分区：
文献类型：
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作者：
Laske, Karoline;Shebzukhov, Yuriy V.;Gouttefangeas, Cecile
最近已将hydin基因的突变描述为导致小鼠中致死性先天性脑积水的一种可能机制，并且提出类似的缺陷涉及人类中常染色体隐性形式的脑积水。在这里，我们首次报告了人类中两种HYDIN变体的癌症相关性和免疫原性。一个是先前描述的来源于1号染色体基因拷贝的序列，即KIAA 1864。第二个是由一种新的替代转录本编码的16号染色体，我们确定了免疫筛选睾丸衍生的cDNA表达文库与大肠癌患者的血清，并称为MO-TES 391。这两种变体在癌症患者的重要子集中被免疫球蛋白G抗体靶向，但在健康供体中很少。此外，我们鉴定了来自MO-TES 391和KIAA 1864的HLA-A*0201限制性序列，其被人细胞毒性CD 8（+）T细胞特异性识别。总之，这些结果表明，在癌症患者中针对HYDIN变体的频繁和协调的适应性免疫应答，并提出HYDIN作为新的癌症相关抗原。(C)2013年AACR。
A mutation in the hydin gene has been recently described as one possible mechanism leading to lethal congenital hydrocephalus in mice, and a similar defect is proposed to be involved in an autosomal recessive form of hydrocephalus in human. Here, we report for the first time on the cancer association and immunogenicity of two HYDIN variants in humans. One is a previously described sequence derived from the chromosome 1 gene copy, that is, KIAA1864. The second is encoded by a novel alternative transcript originating from the chromosome 16, which we identified by immunoscreening of a testis-derived cDNA expression library with sera of patients with colorectal cancer, and called MO-TES391. Both variants are targeted by immunoglobulin G antibodies in a significant subset of cancer patients but only rarely in healthy donors. Moreover, we identify HLA-A*0201-restricted sequences derived from MO-TES391 and KIAA1864, which are specifically recognized by human cytotoxic CD8(+) T cells. Taken together, these results suggest frequent and coordinated adaptive immune responses against HYDIN variants in patients with cancer and propose HYDIN as a novel cancer-associated antigen. (C) 2013 AACR.