Holtappels Rafaela, Podlech Jürgen, Pahl-Seibert Marcus-Folker, Jülch Markus, Thomas Doris, Simon Christian O, Wagner Markus, Reddehase Matthias J
Institute for Virology, Johannes Gutenberg-University, Hochhaus am Augustusplatz, 55101 Mainz, Germany.
J Exp Med. 2004 Jan 5;199(1):131-6. doi: 10.1084/jem.20031582. Epub 2003 Dec 29.
Cytomegaloviruses (CMVs) code for several proteins that inhibit the presentation of antigenic peptides to CD8 T cells. Although the molecular mechanisms of CMV interference with the major histocompatibility complex class I pathway are long understood, surprisingly little evidence exists to support a role in vivo. Here we document the first example of the presentation of an antigenic peptide being blocked by a CMV immune evasion protein in organs relevant to CMV disease. Although this Db-restricted peptide, which is derived from the antiapoptotic protein M45 of murine CMV (mCMV), is classified as an immunodominant peptide based on response magnitude and long-term memory, adoptive transfer of M45 epitope-specific CD8 T cells did not protect against infection with wild-type mCMV. Notably, the same cells protected C57BL/6 mice infected with an mCMV mutant in which immune evasion protein m152/gp40 is deleted. These data indicate that direct presentation or cross-presentation of an antigenic peptide by professional antigen-presenting cells can efficiently prime CD8 T cells that fail in protection against CMV organ disease because m152/gp40 prevents presentation of this peptide in pathogenetically relevant tissue cells.
巨细胞病毒（CMV）编码多种抑制抗原肽呈递给CD8 T细胞的蛋白质。尽管CMV干扰主要组织相容性复合体I类途径的分子机制早已为人所知，但令人惊讶的是，几乎没有证据支持其在体内发挥作用。在此，我们记录了在与CMV疾病相关的器官中，一种抗原肽的呈递首次被CMV免疫逃避蛋白阻断的实例。尽管这种受Db限制的肽源自鼠巨细胞病毒（mCMV）的抗凋亡蛋白M45，基于反应强度和长期记忆被归类为免疫显性肽，但M45表位特异性CD8 T细胞的过继转移并不能预防野生型mCMV感染。值得注意的是，相同的细胞保护了感染缺失免疫逃避蛋白m152/gp40的mCMV突变体的C57BL/6小鼠。这些数据表明，专业抗原呈递细胞对抗原肽的直接呈递或交叉呈递可有效启动CD8 T细胞，这些细胞在预防CMV器官疾病方面失败，因为m152/gp40可阻止该肽在致病相关组织细胞中的呈递。
