Inhibition of cell surface MHC class II expression by Salmonella.
Peptide presentation by MHC molecules is an essential component of the adaptive immune response. To persist in a host, many pathogens have evolved strategies that interfere with MHC antigen-presentation. We show that in human cells harboring intracellular Salmonella, MHC class II cell surface expression was substantially reduced. The effect was specific for MHC class II as expression of additional surface receptors remained unchanged. We investigated the underlying mechanism and showed that class II biosynthesis and peptide loading were unaffected by the presence of Salmonella; however, infection led to an intracellular accumulation of mature molecules. The intracellular class II colocalized with lysosome-associated membrane protein-1 and HLA-DM but not with the Salmonella-containing vacuole. Using Salmonella mutants defective in different components and effectors of the Salmonella pathogenicity island-2 type-III secretion system, we traced the effect on class II to the sifA locus. SifA has been shown to be involved in recruiting membrane for the Salmonella-containing vacuoles. Our data suggest an additional role for SifA in interfering with MHC class II antigen-presentation.
Immunology Division, Department of Pathology, University of Cambridge, Cambridge, GB.
Erin K
EK
Mitchell
Pietro
P
Mastroeni
Adrian P
AP
Kelly
John
J
Trowsdale
D017951:Antigen Presentation; D015703:Antigens, CD / Q000032:analysis; D001426:Bacterial Proteins / Q000502:physiology; D045744:Cell Line, Tumor; D015536:Down-Regulation; D006023:Glycoproteins / Q000502:physiology; D006681:HLA-D Antigens / Q000032:analysis; D000949:Histocompatibility Antigens Class II / Q000032:analysis* / Q000096:biosynthesis; D006801:Humans; D051907:Lysosomal Membrane Proteins; D012475:Salmonella / Q000502:physiology*
D015703:Antigens, CD; D001426:Bacterial Proteins; D006023:Glycoproteins; D006681:HLA-D Antigens; C084245:HLA-DM antigens; D000949:Histocompatibility Antigens Class II; D051907:Lysosomal Membrane Proteins; C421862:SifA protein, Salmonella