Machold R P, Wiertz E J, Jones T R, Ploegh H L
Department of Biology, Massachusetts Institute of Technology, Cambridge 02139, USA.
J Exp Med. 1997 Jan 20;185(2):363-6. doi: 10.1084/jem.185.2.363.
Human cytomegalovirus downregulates the expression of human class I major histocompatibility complex (MHC) molecules by accelerating destruction of newly synthesized class I heavy chains. The HCMV genome contains at least two genes, US11 and US2, each of which encode a product sufficient for causing the dislocation of newly synthesized class I heavy chains from the lumen of the endoplasmic reticulum to the cytosol. Based on a comparison of their abilities to degrade the murine class I molecules H-2Kb, Kd, Db, Dd, and Ld, the US11 and US2 gene products have non-identical specificities for class I molecules. Specifically, in human astrocytoma cells (U373-MG) transfected with the US11 gene, the Kb, Db, Dd, and Ld molecules expressed via recombinant vaccinia virus are rapidly degraded, whereas in US2-transfected cells, only Db and Dd are significantly destabilized. The diversity in HCMV-encoded functions that interfere with class I-restricted presentation likely evolved in response to the polymorphism of the MHC.
人巨细胞病毒通过加速新合成的I类重链的破坏来下调人I类主要组织相容性复合体（MHC）分子的表达。人巨细胞病毒基因组包含至少两个基因，即US11和US2，每个基因编码的产物都足以导致新合成的I类重链从内质网腔移位到细胞质溶胶中。根据它们降解鼠类I类分子H-2Kb、Kd、Db、Dd和Ld能力的比较，US11和US2基因产物对I类分子具有不同的特异性。具体而言，在转染了US11基因的人星形细胞瘤细胞（U373-MG）中，通过重组痘苗病毒表达的Kb、Db、Dd和Ld分子会迅速降解，而在转染了US2的细胞中，只有Db和Dd会明显不稳定。人巨细胞病毒编码的干扰I类限制性呈递的功能多样性可能是为了应对MHC的多态性而进化的。
