Salmonella regulates polyubiquitination and surface expression of MHC class II antigens.
Salmonella typhimurium is a facultative pathogen capable of entering and replicating in both professional and non-professional antigen presenting cells. Control of infection requires MHC class II restricted CD4 T-helper cell responses. Here we show that Salmonella infection induced polyubiquitination of HLA-DR, a post-translational modification that led to removal of mature, peptide loaded, alphabeta dimers from the cell surface. Immature alphabetaIi complexes were unaffected. Surface expression of all class II isotypes, HLA-DP, -DQ, and -DR, was reduced in infected cells, but other cell-surface molecules that traffic through class II peptide loading compartments were unaffected. A Salmonella strain carrying a mutation in ssaV did not induce ubiquitination of class II, implicating Salmonella T3SS-2 effector proteins in the process. T3SS-2 effectors, with established or proposed roles in ubiquitination, were not required for class II down-regulation, suggesting that an additional T3SS-2 effector is involved in regulating MHC class II ubiquitination. Although recognized as a viral immune evasion strategy, here, we demonstrate that bacteria can control surface MHC expression through ubiquitination.
Lapaque
Nicolas
N
Division of Immunology, Department of Pathology, University of Cambridge, Cambridge CB2 1QP, United Kingdom.
Hutchinson
James L
JL
Jones
Des C
DC
Méresse
Stéphane
S
Holden
David W
DW
Trowsdale
John
J
Kelly
Adrian P
AP
D000595:Amino Acid Sequence; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D002469:Cell Separation; D003593:Cytoplasm / Q000378:metabolism; D005434:Flow Cytometry; D015964:Gene Expression Regulation, Bacterial; D006367:HeLa Cells; D000949:Histocompatibility Antigens Class II / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D008969:Molecular Sequence Data; D012475:Salmonella / Q000378:metabolism*; D012480:Salmonella Infections / Q000378:metabolism; D025801:Ubiquitin / Q000378:metabolism*
D000949:Histocompatibility Antigens Class II; D025801:Ubiquitin