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从表达人乳头瘤病毒16型E6癌蛋白的细胞中鉴定出一种天然加工的HLA A0201限制性病毒肽。

Identification of a naturally processed HLA A0201-restricted viral peptide from cells expressing human papillomavirus type 16 E6 oncoprotein.

作者信息

Bartholomew J S, Stacey S N, Coles B, Burt D J, Arrand J R, Stern P L

机构信息

Department of Immunology, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Manchester, GB.

出版信息

Eur J Immunol. 1994 Dec;24(12):3175-9. doi: 10.1002/eji.1830241239.

Abstract

Human papillomavirus (HPV) DNA encoding the oncogenic proteins E6 and E7 is usually retained in cervical carcinomas, implicating these proteins as potential target antigens for immune recognition in this virally associated tumor. We have characterized endogenously processed peptides eluted from major histocompatibility complex class I molecules in cells infected with a recombinant vaccinia expressing the HPV-16 E6 oncoprotein. The reverse-phase chromatography profile of peptides eluted from isolated HLA-A0201 molecules in cells expressing the E6 oncoprotein differs from that of cells not expressing E6. Sequential Edman degradation of novel peaks found in the peptide profiles from cells expressing HPV-16 E6 led to the identification of a naturally processed HLA-A0201-restricted E6 peptide of sequence KLPQLCTEL. This approach has allowed the identification of a viral peptide which is processed and presented by cells expressing the E6 oncoprotein and is a likely target for cytotoxic T lymphocyte recognition in HLA-A0201-positive patients.

摘要

编码致癌蛋白E6和E7的人乳头瘤病毒(HPV)DNA通常保留在宫颈癌中,这表明这些蛋白是这种病毒相关肿瘤中免疫识别的潜在靶抗原。我们已对从感染了表达HPV-16 E6致癌蛋白的重组痘苗病毒的细胞中,从主要组织相容性复合体I类分子上洗脱下来的内源性加工肽进行了表征。从表达E6致癌蛋白的细胞中分离出的HLA-A0201分子上洗脱的肽的反相色谱图谱,与未表达E6的细胞不同。对表达HPV-16 E6的细胞的肽谱中发现的新峰进行连续的埃德曼降解,从而鉴定出序列为KLPQLCTEL的天然加工的HLA-A0201限制性E6肽。这种方法已能够鉴定出一种病毒肽,该肽由表达E6致癌蛋白的细胞加工并呈递,并且很可能是HLA-A0201阳性患者中细胞毒性T淋巴细胞识别的靶标。

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