Inhibition of cellular alpha-glucosidases results in increased presentation of hepatitis B virus glycoprotein-derived peptides by MHC class I.
Inhibitors of alpha glucosidases prevent the trimming of oligosaccharides on certain nascent glycoproteins, including the hepatitis B virus MHBs envelope glycoprotein. MHBs proteins with untrimmed oligosaccharides do not interact with calnexin, increasing protein misfolding and subsequent degradation by proteasomes. As peptides loaded onto newly synthesized MHC class I complexes are predominantly derived from proteasomes, the possibility that glucosidase inhibition could increase presentation by MHC class I was determined. Using either a model epitope, or a natural MHBs epitope, it was demonstrated that glucosidase inhibitors enhanced presentation by MHC class I and promoted activation of antigen-specific CTLs, suggesting a pharmacologic approach to immune modulation.
Simsek
Ender
E
Department of Microbiology and Immunology, Drexel Institute for Biotechnology and Virology Research, Drexel University College of Medicine, Doylestown, PA 18902, USA.
Sinnathamby
Gomathinayagam
G
Block
Timothy M
TM
Liu
Yuanjie
Y
Philip
Ramila
R
Mehta
Anand S
AS
Norton
Pamela A
PA
D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D016679:Genome, Viral; D006515:Hepatitis B virus / Q000235:genetics / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D007739:L Cells; D008285:Major Histocompatibility Complex; D051379:Mice; D008969:Molecular Sequence Data; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014162:Transfection; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000276:immunology; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology; D000520:alpha-Glucosidases / Q000302:isolation & purification*
D015395:Histocompatibility Antigens Class I; D014759:Viral Envelope Proteins; D014764:Viral Proteins; D000520:alpha-Glucosidases