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利用重组腺病毒载体和合成肽鉴定单纯疱疹病毒糖蛋白B中免疫显性细胞毒性T淋巴细胞识别位点

Identification of an immunodominant cytotoxic T-lymphocyte recognition site in glycoprotein B of herpes simplex virus by using recombinant adenovirus vectors and synthetic peptides.

作者信息

Hanke T, Graham F L, Rosenthal K L, Johnson D C

机构信息

Department of Pathology, McMaster University, Hamilton, Ontario, Canada.

出版信息

J Virol. 1991 Mar;65(3):1177-86. doi: 10.1128/JVI.65.3.1177-1186.1991.

DOI:10.1128/JVI.65.3.1177-1186.1991
PMID:1847447
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC239884/
Abstract

Cytotoxic T-lymphocyte (CTL) responses to herpes simplex virus (HSV) polypeptides play an important role in recovery from infection and in preventing latency. We have previously shown that glycoprotein B (gB) is a major target recognized by HSV-specific CTLs in C57BL/6 (H-2b) and BALB/c (H-2d) mice but not in CBA/J (H-2k) mice (L. A. Witmer, K. L. Rosenthal, F. L. Graham, H. M. Friedman, A. Yee, and D. C. Johnson, J. Gen. Virol. 71:387-396, 1990). In this report, we utilize adenovirus vectors expressing gB with various deletions to localize an immunodominant site in gB, recognized by H-2b-restricted anti-HSV CTLs, to a region between residues 462 and 594. Overlapping peptides spanning this region were synthesized and used to further localize the immunodominant site to residues 489 to 515, a region highly conserved in HSV type 1 (HSV-1) and HSV-2 strains. The 11-amino-acid peptide was apparently associated exclusively with the Kb major histocompatibility complex gene product and not the Db gene product. In contrast, H-2d-restricted CTLs recognized an immunodominant site between residues 233 and 379.

摘要

细胞毒性T淋巴细胞(CTL)对单纯疱疹病毒(HSV)多肽的反应在感染恢复和预防潜伏中起重要作用。我们之前已经表明,糖蛋白B(gB)是C57BL/6(H-2b)和BALB/c(H-2d)小鼠中HSV特异性CTL识别的主要靶标,但在CBA/J(H-2k)小鼠中不是(L.A. Witmer、K.L. Rosenthal、F.L. Graham、H.M. Friedman、A. Yee和D.C. Johnson,《病毒学杂志》71:387 - 396,1990年)。在本报告中,我们利用表达具有各种缺失的gB的腺病毒载体,将H-2b限制性抗HSV CTL识别的gB中的免疫显性位点定位到462至594位残基之间的区域。合成了跨越该区域的重叠肽,并用于将免疫显性位点进一步定位到489至515位残基,这是1型单纯疱疹病毒(HSV-1)和2型单纯疱疹病毒(HSV-2)毒株中高度保守的区域。这个11个氨基酸的肽显然仅与Kb主要组织相容性复合体基因产物相关,而与Db基因产物无关。相比之下,H-2d限制性CTL识别233至379位残基之间的一个免疫显性位点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8105/239884/59d8fd334cae/jvirol00046-0139-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8105/239884/59d8fd334cae/jvirol00046-0139-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8105/239884/59d8fd334cae/jvirol00046-0139-a.jpg

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单纯疱疹病毒 1 通过表达鼠源 CD80 替代潜伏相关转录物 (LAT) 可补偿 LAT 的潜伏再激活和抗凋亡功能。
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