title: Human immune response to streptococcal inhibitor of complement, a serotype M1 group A Streptococcus extracellular protein involved in epidemics.
abstract: Streptococcal inhibitor of complement (Sic) is a highly polymorphic extracellular protein made by serotype M1 group A Streptococcus strains that contributes to bacterial persistence in the mammalian upper respiratory tract. New variants of the Sic protein arise very rapidly by positive selection in human populations during M1 epidemics. The human antibody response to Sic was analyzed. Of 636 persons living in diverse localities, 43% had anti-Sic serum antibodies, but only 16.4% had anti-M1 protein serum antibody. Anti-Sic antibody was also present in nasal wash specimens in high frequency. Linear B cell epitope mapping showed that serum antibodies recognized epitopes located in structurally variable regions of Sic and the amino terminal hypervariable region of the M1 protein. Phage display analyses confirmed that the polymorphic regions of Sic are primary targets of host antibodies. These results support the hypothesis that selection of Sic variants occurs on mucosal surfaces by a mechanism that involves acquired host antibody.
authors.affiliation: Laboratory of Human Bacterial Pathogenesis, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA. nhoe@niaid.nih.gov
authors.forename: N P
authors.initials: NP
authors.lastname: Hoe
authors.forename: P
authors.initials: P
authors.lastname: Kordari
authors.forename: R
authors.initials: R
authors.lastname: Cole
authors.forename: M
authors.initials: M
authors.lastname: Liu
authors.forename: T
authors.initials: T
authors.lastname: Palzkill
authors.forename: W
authors.initials: W
authors.lastname: Huang
authors.forename: D
authors.initials: D
authors.lastname: McLellan
authors.forename: G J
authors.initials: GJ
authors.lastname: Adams
authors.forename: M
authors.initials: M
authors.lastname: Hu
authors.forename: J
authors.initials: J
authors.lastname: Vuopio-Varkila
authors.forename: T R
authors.initials: TR
authors.lastname: Cate
authors.forename: M E
authors.initials: ME
authors.lastname: Pichichero
authors.forename: K M
authors.initials: KM
authors.lastname: Edwards
authors.forename: J
authors.initials: J
authors.lastname: Eskola
authors.forename: D E
authors.initials: DE
authors.lastname: Low
authors.forename: J M
authors.initials: JM
authors.lastname: Musser
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000595:Amino Acid Sequence; D000907:Antibodies, Bacterial / Q000097:blood; D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins / Q000276:immunology* / Q000378:metabolism; D002352:Carrier Proteins / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D003169:Complement Inactivator Proteins / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D018604:Epitope Mapping; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007223:Infant; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D012703:Serotyping; D013297:Streptococcus pyogenes / Q000145:classification / Q000276:immunology*
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D002352:Carrier Proteins; D003169:Complement Inactivator Proteins; D007074:Immunoglobulin G; C097739:SIC protein, Streptococcus; C014689:streptococcal M protein