Hengel H, Lucin P, Jonjić S, Ruppert T, Koszinowski U H
Department of Virology, University of Heidelberg, Germany.
J Virol. 1994 Jan;68(1):289-97. doi: 10.1128/JVI.68.1.289-297.1994.
An immediate-early protein of murine cytomegalovirus (MCMV), pp89, elicits an immunodominant and protective major histocompatibility complex (MHC) class I Ld-restricted CD8+ T-lymphocyte response. Remarkably, presentation of the naturally processed peptide of pp89, the nonapeptide YPHFMPTNL, is abolished during permissive MCMV infection in vitro. This defect in pp89 presentation is due to the expression of MCMV early gene functions that specifically block the transport of peptide-charged MHC class I complexes to the cell surface (M. Del Val, H. Hengel, H. Häcker, U. Hartlaub, T. Ruppert, P. Lucin, and U. H. Koszinowski, J. Exp. Med. 176:729-738, 1992). Here, we demonstrate that MCMV-specific CD8+ T lymphocytes can reconstitute pp89 presentation in a parakrine fashion. The lymphocytes mediate the restoration of antigen presentation by MCMV-infected cells by releasing gamma interferon (IFN-gamma). IFN-gamma has no effect on synthesis and stability of the viral antigen pp89 nor does it interfere with the expression of viral early genes and their inhibitory effect on MHC class I molecular maturation. IFN-gamma results in a 25-fold increase in the synthesis of MHC class I molecules and a similar increase in the abundance of pp89-derived peptide. Many of the MHC molecules remain retained by the viral effect, but a surplus of MHC molecules escapes the effect and provides the effective surface presentation of the peptide. Adoptive cell transfer studies demonstrate the IFN-gamma dependence of CD8+ T-lymphocyte function in vivo. Altogether, these data reconcile the paradoxical findings of an impaired pp89 presentation in vitro in parallel with pp89-specific CD8+ T-cell protection in vivo. The results also imply a role of IFN-gamma in the T-lymphocyte-mediated control of cytomegalovirus infection. The known propensity of cytomegalovirus to cause serious disease in the immunocompromised host is discussed in the light of these findings.
小鼠巨细胞病毒（MCMV）的一种立即早期蛋白pp89，可引发免疫显性且具有保护性的主要组织相容性复合体（MHC）I类Ld限制性CD8 + T淋巴细胞反应。值得注意的是，在体外允许性MCMV感染期间，pp89天然加工肽（九肽YPHFMPTNL）的呈递被消除。pp89呈递的这种缺陷是由于MCMV早期基因功能的表达，该功能特异性地阻断了带肽的MHC I类复合体向细胞表面的转运（M. Del Val、H. Hengel、H. Häcker、U. Hartlaub、T. Ruppert、P. Lucin和U. H. Koszinowski，《实验医学杂志》176:729 - 738，1992年）。在此，我们证明MCMV特异性CD8 + T淋巴细胞可以旁分泌方式重建pp89呈递。这些淋巴细胞通过释放γ干扰素（IFN - γ）介导MCMV感染细胞对抗原呈递的恢复。IFN - γ对病毒抗原pp89的合成和稳定性没有影响，也不干扰病毒早期基因的表达及其对MHC I类分子成熟的抑制作用。IFN - γ导致MHC I类分子的合成增加25倍，并且pp89衍生肽的丰度也有类似增加。许多MHC分子仍受病毒效应的保留，但有多余的MHC分子逃脱该效应并提供肽的有效表面呈递。过继性细胞转移研究证明了体内CD8 + T淋巴细胞功能对IFN - γ的依赖性。总之，这些数据解释了体外pp89呈递受损与体内pp89特异性CD8 + T细胞保护这一矛盾发现。结果还暗示了IFN - γ在T淋巴细胞介导的巨细胞病毒感染控制中的作用。根据这些发现讨论了巨细胞病毒在免疫受损宿主中引起严重疾病的已知倾向。
