特异于内源性逆转录病毒 ERV-K-Env 中 HLA-A*03:01 限制性表位的 T 细胞受体对其同源表位的识别能力有限。

IF 4.7 2区 生物学 Q1 GENETICS & HEREDITY
Erin E Grundy, Lauren C Shaw, Loretta Wang, Abigail V Lee, James Castro Argueta, Daniel J Powell, Mario Ostrowski, R Brad Jones, C Russell Y Cruz, Heather Gordish-Dressman, Nicole P Chappell, Catherine M Bollard, Katherine B Chiappinelli
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引用次数: 0

摘要

可转座元件(TE)在肿瘤细胞中的表达水平往往高于正常细胞,这意味着这些基因组区域是一个尚未开发的肿瘤相关抗原库。在卵巢癌(OC)中,肿瘤细胞经常表达来自TE ERV-K的蛋白。在这里,我们确定了先前确定的 ERV-K 包膜基因(env)表位是否会导致针对癌细胞的靶抗原特异性。我们发现,用ERV-K-Env特异性T细胞受体构建体转导健康供体T细胞,只有在与HLA-A*03:01 B淋巴母细胞共培养时才会产生抗原特异性。此外,用ERV-K-Env的这一表位对几名健康供体进行体外引物诱导,也没有产生目标抗原特异性。这些数据表明,T细胞受体在靶向这一特异性ERV-K-Env表位方面并不理想,作为治疗OC的T细胞疗法的潜力有限。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
A T cell receptor specific for an HLA-A*03:01-restricted epitope in the endogenous retrovirus ERV-K-Env exhibits limited recognition of its cognate epitope.

Transposable elements (TEs) are often expressed at higher levels in tumor cells than normal cells, implicating these genomic regions as an untapped pool of tumor-associated antigens. In ovarian cancer (OC), protein from the TE ERV-K is frequently expressed by tumor cells. Here we determined whether the targeting of previously identified epitope in the envelope gene (env) of ERV-K resulted in target antigen specificity against cancer cells. We found that transducing healthy donor T cells with an ERV-K-Env-specific T cell receptor construct resulted in antigen specificity only when co-cultured with HLA-A*03:01 B lymphoblastoid cells. Furthermore, in vitro priming of several healthy donors with this epitope of ERV-K-Env did not result in target antigen specificity. These data suggest that the T cell receptor is a poor candidate for targeting this specific ERV-K-Env epitope and has limited potential as a T cell therapy for OC.

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来源期刊
Mobile DNA
Mobile DNA GENETICS & HEREDITY-
CiteScore
8.20
自引率
6.10%
发文量
26
审稿时长
11 weeks
期刊介绍: Mobile DNA is an online, peer-reviewed, open access journal that publishes articles providing novel insights into DNA rearrangements in all organisms, ranging from transposition and other types of recombination mechanisms to patterns and processes of mobile element and host genome evolution. In addition, the journal will consider articles on the utility of mobile genetic elements in biotechnological methods and protocols.
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