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在缅甸猕猴原发性猴免疫缺陷病毒感染期间,主要组织相容性复合体 I 类限制的细胞毒性 T 淋巴细胞反应。

Major histocompatibility complex class I-restricted cytotoxic T lymphocyte responses during primary simian immunodeficiency virus infection in Burmese rhesus macaques.

机构信息

Division for AIDS Vaccine Development, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.

出版信息

Microbiol Immunol. 2011 Nov;55(11):768-73. doi: 10.1111/j.1348-0421.2011.00384.x.

Abstract

Major histocompatibility complex class I (MHC-I)-restricted CD8(+) cytotoxic T lymphocyte (CTL) responses are crucial for the control of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) replication. In particular, Gag-specific CTL responses have been shown to exert strong suppressive pressure on HIV/SIV replication. Additionally, association of Vif-specific CTL frequencies with in vitro anti-SIV efficacy has been suggested recently. Host MHC-I genotypes could affect the immunodominance patterns of these potent CTL responses. Here, Gag- and Vif-specific CTL responses during primary SIVmac239 infection were examined in three groups of Burmese rhesus macaques, each group having a different MHC-I haplotype. The first group of four macaques, which possessed the MHC-I haplotype 90-010-Ie, did not show Gag- or Vif-specific CTL responses. However, Nef-specific CTL responses were elicited, suggesting that primary SIV infection does not induce predominant CTL responses specific for Gag/Vif epitopes restricted by 90-010-Ie-derived MHC-I molecules. In contrast, Gag- and Vif-specific CTL responses were induced in the second group of two 89-075-Iw-positive animals and the third group of two 91-010-Is-positive animals. Considering the potential of prophylactic vaccination to affect CTL immunodominance post-viral exposure, these groups of macaques would be useful for evaluation of vaccine antigen-specific CTL efficacy against SIV infection.

摘要

主要组织相容性复合体 I 类(MHC-I)限制性 CD8(+)细胞毒性 T 淋巴细胞(CTL)应答对于控制人类免疫缺陷病毒(HIV)和猴免疫缺陷病毒(SIV)复制至关重要。特别是,Gag 特异性 CTL 应答已被证明对 HIV/SIV 复制具有强大的抑制作用。此外,最近有人提出,Vif 特异性 CTL 频率与体外抗 SIV 功效相关。宿主 MHC-I 基因型可能会影响这些强效 CTL 应答的免疫优势模式。在这里,在三组缅甸猕猴中检查了原发性 SIVmac239 感染期间的 Gag 和 Vif 特异性 CTL 应答,每组猕猴具有不同的 MHC-I 单倍型。第一组四只猕猴携带 MHC-I 单倍型 90-010-Ie,未显示 Gag 或 Vif 特异性 CTL 应答。然而,诱导了 Nef 特异性 CTL 应答,表明原发性 SIV 感染不会诱导主要由 90-010-Ie 衍生的 MHC-I 分子限制的 Gag/Vif 表位特异性 CTL 应答。相比之下,在第二组两只 89-075-Iw 阳性动物和第三组两只 91-010-Is 阳性动物中诱导了 Gag 和 Vif 特异性 CTL 应答。考虑到预防性疫苗接种在病毒暴露后影响 CTL 免疫优势的潜力,这些组的猕猴将有助于评估针对 SIV 感染的疫苗抗原特异性 CTL 功效。

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