Human Immune Response to Streptococcal Inhibitor of Complement, a Serotype M1 Group A Streptococcus Extracellular Protein Involved in Epidemics

• Published in: The Journal of infectious diseases 2000-11, Vol.182 (5), p.1425-1436
• Main Authors: Hoe, Nancy P., Kordari, Parichher, Cole, Robert, Liu, Mengyao, Palzkill, Timothy, Huang, Wanzhi, McLellan, Duncan, Adams, Gerald J., Hu, Mary, Vuopio-Varkila, Jaana, Cate, Thomas R., Pichichero, Michael E., Edwards, Kathryn M., Eskola, Juhani, Low, Donald E., Musser, James M.
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Amino Acid Sequence; Amino acids; Antibodies; Antibodies, Bacterial - blood; Antigens, Bacterial; Bacterial Outer Membrane Proteins; Bacterial Proteins - immunology; Bacterial Proteins - metabolism; Bacteriology; Bacteriophages; Biological and medical sciences; Carrier Proteins - immunology; Child; Child, Preschool; Complement Inactivator Proteins - immunology; Enzyme-Linked Immunosorbent Assay; Epidemiology; Epitope Mapping; Epitopes; Female; Fundamental and applied biological sciences. Psychology; Hoes; Humans; Immunoglobulin G - blood; Infant; Infections; Major Articles; Male; Microbiology; Middle Aged; Molecular Sequence Data; Pathogenicity, virulence, toxins, bacteriocins, pyrogens, host-bacteria relations, miscellaneous strains; Room temperature; Serotyping; Sic protein; Streptococcus; Streptococcus pyogenes - classification; Streptococcus pyogenes - immunology
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1086/315882

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.