title: Human CD1d molecules are resistant to human cytomegalovirus US2- and US11-mediated degradation.
abstract: Natural killer T (NKT) cells may play a crucial role in controlling viral infection by bridging the innate and adaptive immune systems. These cells are activated by lipids presented by CD1d molecules, which are structurally homologous to major histocompatibility complex class I (MHC-I) molecules. Although human cytomegalovirus (HCMV) can avoid T cell recognition by down-regulating MHC-I-mediated antigen presentation, it remains unknown whether it can also interfere with CD1d-mediated lipid presentation. Here, we show that CD1d is resistant to rapid degradation induced by the HCMV gene products US2 and US11, which cause dislocation of MHC-I molecules from the endoplasmic reticulum (ER) to the cytosol for destruction by proteasomes. The resistance of CD1d to US11 is mainly due to the short cytosolic tail of CD1d; a hybrid CD1d protein, whose cytosolic tail was replaced with that of HLA-A2.1, was efficiently degraded by US11. Finally, we found that HCMV infection did not significantly influence the cell surface expression of CD1d. Thus, these results suggest that antigen presentation by CD1d is largely unaffected by the multiple immune-modulating functions of HCMV.
authors.affiliation: Cell Dynamics Research Center, School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju 500-712, Republic of Korea.
authors.forename: Sunglim
authors.initials: S
authors.lastname: Cho
authors.forename: Youngsoo
authors.initials: Y
authors.lastname: Jun
mesh_terms: D017951:Antigen Presentation; D055610:Antigens, CD1d / Q000276:immunology / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D003587:Cytomegalovirus / Q000276:immunology / Q000378:metabolism*; D003586:Cytomegalovirus Infections / Q000276:immunology / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D047468:Immunoprecipitation; D016601:RNA-Binding Proteins / Q000276:immunology / Q000378:metabolism*; D014759:Viral Envelope Proteins / Q000276:immunology / Q000378:metabolism*; D014764:Viral Proteins / Q000276:immunology / Q000378:metabolism*
chemical_list: D055610:Antigens, CD1d; C526877:CD1D protein, human; D016601:RNA-Binding Proteins; C074546:US11 protein, herpesvirus; C118670:US2 protein, Varicellovirus; D014759:Viral Envelope Proteins; D014764:Viral Proteins