del Val M, Hengel H, Häcker H, Hartlaub U, Ruppert T, Lucin P, Koszinowski U H
Department of Virology, University of Ulm, Germany.
J Exp Med. 1992 Sep 1;176(3):729-38. doi: 10.1084/jem.176.3.729.
Selective expression of murine cytomegalovirus (MCMV) immediate-early (IE) genes leads to the presentation by the major histocompatibility complex (MHC) class I molecule Ld of a peptide derived from MCMV IE protein pp89 (Reddehase, M.J., J. B. Rothbard, and U.H. Koszinowski. 1989. Nature (Lond.). 337:651). Characterization of endogenous antigenic peptides identified the pp89 peptide as the nonapeptide 168YPHFMPTNL176 (del Val, M., H.-J. Schlicht, T. Ruppert, M.J. Reddehase, and U.H. Koszinowski. 1991. Cell. 66:1145). Subsequent expression of MCMV early genes prevents presentation of pp89 (del Val, M., K. Münch, M.J. Reddehase, and U.H. Koszinowski. 1989. Cell. 58:305). We report on the mechanism by which MCMV early genes interfere with antigen presentation. Expression of the IE promoter-driven bacterial gene lacZ by recombinant MCMV subjected antigen presentation of beta-galactosidase to the same control and excluded antigen specificity. The Ld-dependent presence of naturally processed antigenic peptides also in nonpresenting cells located the inhibitory function subsequent to the step of antigen processing. The finding that during the E phase of MCMV gene expression the MHC class I heavy chain glycosylation remained in an Endo H-sensitive form suggested a block within the endoplasmic reticulum/cis-Golgi compartment. The failure to present antigenic peptides was explained by a general retention of nascent assembled trimolecular MHC class I complexes. Accordingly, at later stages of infection a significant decrease of surface MHC class I expression was seen, whereas other membrane glycoproteins remained unaffected. Thus, MCMV E genes endow this virus with an effective immune evasion potential. These results also indicate that the formation of the trimolecular complex of MHC class I heavy chain, beta 2-microglobulin, and the finally trimmed peptide is completed before entering the medial-Golgi compartment.
小鼠巨细胞病毒（MCMV）立即早期（IE）基因的选择性表达导致主要组织相容性复合体（MHC）I类分子Ld呈递源自MCMV IE蛋白pp89的肽段（雷德哈泽，M.J.，J.B.罗斯巴德，和U.H.科斯齐诺夫斯基。1989年。《自然》（伦敦）。337:651）。内源性抗原肽的特性鉴定表明，pp89肽段为九肽168YPHFMPTNL176（德尔瓦尔，M.，H.-J.施利希特，T.鲁珀特，M.J.雷德哈泽，和U.H.科斯齐诺夫斯基。1991年。《细胞》。66:1145）。随后MCMV早期基因的表达阻止了pp89的呈递（德尔瓦尔，M.，K.明希，M.J.雷德哈泽，和U.H.科斯齐诺夫斯基。1989年。《细胞》。58:305）。我们报告了MCMV早期基因干扰抗原呈递的机制。重组MCMV对IE启动子驱动的细菌基因lacZ的表达使β-半乳糖苷酶的抗原呈递受到相同的调控，并排除了抗原特异性。在非呈递细胞中也存在自然加工的抗原肽依赖于Ld，这表明抑制功能发生在抗原加工步骤之后。在MCMV基因表达的E期，MHC I类重链糖基化仍处于内切糖苷酶H敏感形式，这一发现提示在内质网/顺式高尔基体区室存在阻断。未能呈递抗原肽是由于新生组装的三分子MHC I类复合物普遍滞留所致。因此，在感染后期，表面MHC I类表达显著下降，而其他膜糖蛋白不受影响。因此，MCMV E基因赋予该病毒有效的免疫逃避潜能。这些结果还表明，MHC I类重链、β2-微球蛋白和最终修剪后的肽段的三分子复合物在进入中间高尔基体区室之前就已形成。
