The HCMV gene products US11 and US2 differ in their ability to attack allelic forms of murine major histocompatibility complex (MHC) class I heavy chains - PubMed (original) (raw)

The HCMV gene products US11 and US2 differ in their ability to attack allelic forms of murine major histocompatibility complex (MHC) class I heavy chains

R P Machold et al. J Exp Med. 1997.

Abstract

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.

PubMed Disclaimer

Figures

Figure 2

The Kb degradation intermediate is a deglycosylated heavy chain. US11+ cells were infected with vaccinia virus expressing H-2Kb (lacking cytoplasmic tail), labeled for 10 min with [35S]methionine, and chased as indicated. Immunoprecipitated Kb heavy chains from each chase point were either kept on ice (−) or treated with recombinant _N_-glycanase (+) before resolution by SDS-PAGE (A) or 1D-IEF (B).

Figure 1

Fate of murine class I MHC heavy chains in US11+ or US2+ cells. Control (nontransfected), US11+, or US2+ cells were infected with vaccinia virus expressing H-2Kb (lacking the cytoplasmic tail; A), Kd (B), Db (C), Dd (D), or Ld (E), labeled with [35S]methionine for 10 min and chased as indicated. Immunoprecipitated murine class I molecules were resolved on a 12.5% SDS–polyacrylamide gel and visualized by fluorography. The position of the breakdown intermediate is indicated with an asterisk.

References

1. Yewdell JW, Bennink JR. Cell biology of antigen processing and presentation to MHC class I molecule- restricted T lymphocytes. Adv Immunol. 1992;52:1–123. - PubMed
1. Burgert HG, Kvist S. An adenovirus type 2 glycoprotein blocks cell surface expression of human histocompatibility class I antigens. Cell. 1985;41:987–997. - PubMed
1. York IA, Roop C, Andrews DW, Riddell SR, Graham FL, Johnson DC. A cytosolic herpes simplex virus protein inhibits antigen presentation to CD8+T lymphocytes. Cell. 1994;77:525–535. - PubMed
1. Del Val M, Hengel H, Hacker H, Hartlaub U, Ruppert T, Lucin P, Koszinowski UH. Cytomegalovirus prevents antigen presentation by blocking transport of peptide-loaded major histocompatibility complex class I molecules into the medial Golgi compartment. J Exp Med. 1992;176:729–738. - PMC - PubMed
1. Browne HG, Smith G, Beck S, Minson T. A complex between the MHC homologue encoded by human cytomegalovirus and b2-microglobulin. Nature (Lond) 1990;347:770–772. - PubMed

The HCMV gene products US11 and US2 differ in their ability to attack allelic forms of murine major histocompatibility complex (MHC) class I heavy chains - PubMed (original) (raw)