Human cytomegalovirus gene products US2 and US11 differ in their ability to attack major histocompatibility class I heavy chains in dendritic cells.
Human cytomegalovirus (HCMV) encodes several proteins that inhibit major histocompatibility complex (MHC) class I-dependent antigen presentation. The HCMV products US2 and US11 are each sufficient for causing the dislocation of human and murine MHC class I heavy chains from the lumen of the endoplasmic reticulum to the cytosol, where the heavy chains are readily degraded. The apparent redundancy of US2 and US11 has been probed predominantly in cultured cell lines, where differences in their specificities were shown for murine and human MHC class I locus products. Here, we expressed US11 and US2 via adenovirus vectors and show that US11 exhibits a superior ability to degrade MHC class I molecules in primary human dendritic cells. MHC class II complexes are unaffected by US2- and US11-mediated attack. We suggest that multiple HCMV-encoded immunoevasions have evolved complementary functions in response to diverse host cell types and tissues.
Rehm
Armin
A
Robert-Rössle-Klinik, Department of Hematology, Oncology and Tumorimmunology, Universitätsklinikum Charite, Max Delbrück Center for Molecular Medicine, Berlin, Germany. arehm@mdc-berlin.de
Engelsberg
Arne
A
Tortorella
Domenico
D
Körner
Ida J
IJ
Lehmann
Insa
I
Ploegh
Hidde L
HL
Höpken
Uta E
UE
D000256:Adenoviridae / Q000235:genetics; D002478:Cells, Cultured; D003587:Cytomegalovirus / Q000378:metabolism*; D003713:Dendritic Cells / Q000276:immunology*; D015536:Down-Regulation; D005822:Genetic Vectors; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006801:Humans; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D014161:Transduction, Genetic; D014759:Viral Envelope Proteins / Q000235:genetics / Q000378:metabolism*; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*
D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D016601:RNA-Binding Proteins; C074546:US11 protein, herpesvirus; C118670:US2 protein, Varicellovirus; D014759:Viral Envelope Proteins; D014764:Viral Proteins