title: Peptidoglycan-linked protein A promotes T cell-dependent antibody expansion during Staphylococcus aureus infection.
abstract: A hallmark of Staphylococcus aureus disease in humans is persistent infections without development of protective immune responses. Infected patients generate VH3 plasmablast expansions and increased VH3 idiotype Ig; however, the mechanisms for staphylococcal modification of immune responses are not known. We report here that S. aureus-infected mice generate VH3 antibody expansions via a mechanism requiring MHC-restricted antigen presentation to CD4(+) T cells and staphylococcal protein A (SpA), a cell wall-anchored surface molecule that binds Fcγ and VH3 variant heavy chains of Ig. VH3 expansion occurred with peptidoglycan-linked SpA from the bacterial envelope but not with recombinant SpA, and optimally required five tandem repeats of its Ig-binding domains. Signaling via receptor-interacting serine/threonine protein kinase 2 (RIPK2) was essential for implementing peptidoglycan-linked SpA superantigen activity. VH3 clan IgG from S. aureus-infected or SpA-treated animals was not pathogen-specific, suggesting that SpA cross-linking of VH3 idiotype B-cell receptors and activation via attached peptidoglycan are the determinants of staphylococcal escape from adaptive immune responses.
authors.affiliation: Department of Microbiology, University of Chicago, Chicago, IL 60637.
authors.forename: Hwan Keun
authors.initials: HK
authors.lastname: Kim
authors.affiliation: Department of Microbiology, University of Chicago, Chicago, IL 60637.
authors.forename: Fabiana
authors.initials: F
authors.lastname: Falugi
authors.affiliation: Department of Microbiology, University of Chicago, Chicago, IL 60637.
authors.forename: Dominique M
authors.initials: DM
authors.lastname: Missiakas
authors.affiliation: Department of Microbiology, University of Chicago, Chicago, IL 60637 oschnee@bsd.uchicago.edu.
authors.forename: Olaf
authors.initials: O
authors.lastname: Schneewind
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis* / Q000097:blood; D000917:Antibody Formation; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010457:Peptidoglycan / Q000276:immunology; D013203:Staphylococcal Infections / Q000097:blood / Q000276:immunology* / Q000382:microbiology; D013205:Staphylococcal Protein A / Q000276:immunology*; D013211:Staphylococcus aureus / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology
chemical_list: D000907:Antibodies, Bacterial; D010457:Peptidoglycan; D013205:Staphylococcal Protein A
keywords: B-cell superantigen; RIPK2; T cell; VH3 clonal antibody; staphylococcal protein A