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DNA免疫可在H-2b小鼠中诱导针对乙肝核心抗原的抗体和细胞毒性T细胞反应。

DNA immunization induces antibody and cytotoxic T cell responses to hepatitis B core antigen in H-2b mice.

作者信息

Kuhöber A, Pudollek H P, Reifenberg K, Chisari F V, Schlicht H J, Reimann J, Schirmbeck R

机构信息

Department of Medical Microbiology, University of Ulm, Germany.

出版信息

J Immunol. 1996 May 15;156(10):3687-95.

PMID:8621903
Abstract

The serum Ab response and the class I-restricted CTL response of C57BL/6 (H-2b) mice to hepatitis B (pre)core Ag (HBcAg, HBeAg) was studied. Injection of HBcAg particles without adjuvants into mice efficiently primed serum Ab responses but not CTL response. We constructed the expression plasmids pCMV-1/c and pCMV-1/e in which expression of HBcAg or HBeAg was driven by cytomegalovirus immediate early region promoter sequences. Stable murine RBL5/C transfectant lines expressing HBcAg were established. Intramuscular DNA immunization with plasmid pCMV-1/c (encoding intracellularly expressed core Ag) or pCMV-1/e (encoding secreted precore Ag) efficiently primed specific serum Ab responses and CTL responses. The CTL response elicited in this system was mediated by CD4-CD8+ effector cells primed in vivo. The CTL recognized the HBcAg93-100 8-mer peptide MGLKFRQL in the context of Kb. Hence, DNA immunization with HBcAg/HBeAg-expressing plasmids, but not immunization with exogenous HBcAg particles, elicits a class I-restricted CTL response of defined epitope/restriction specificity in H-2b mice.

摘要

研究了C57BL/6(H-2b)小鼠对乙型肝炎(前)核心抗原(HBcAg、HBeAg)的血清抗体反应和I类限制性细胞毒性T淋巴细胞(CTL)反应。将无佐剂的HBcAg颗粒注射到小鼠体内可有效引发血清抗体反应,但不能引发CTL反应。我们构建了表达质粒pCMV-1/c和pCMV-1/e,其中HBcAg或HBeAg的表达由巨细胞病毒立即早期区域启动子序列驱动。建立了稳定表达HBcAg的鼠RBL5/C转染细胞系。用质粒pCMV-1/c(编码细胞内表达的核心抗原)或pCMV-1/e(编码分泌的前核心抗原)进行肌肉内DNA免疫可有效引发特异性血清抗体反应和CTL反应。该系统中引发的CTL反应由体内引发的CD4-CD8+效应细胞介导。CTL在Kb背景下识别HBcAg93-100 8聚体肽MGLKFRQL。因此,用表达HBcAg/HBeAg的质粒进行DNA免疫,而不是用外源性HBcAg颗粒进行免疫,可在H-2b小鼠中引发具有确定表位/限制性特异性的I类限制性CTL反应。

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