Human immune response to streptococcal inhibitor of complement, a serotypeM1 group A Streptococcus extracellular protein involved in epidemics

Streptococcal inhibitor of complement (Sic) is a highly polymorphic extrace llular protein made by serotype M1 group A Streptococcus strains that contr ibutes to bacterial persistence in the mammalian upper respiratory tract. N ew variants of the Sic protein arise very rapidly by positive selection in human populations during M1 epidemics. The human antibody response to Sic w as 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-S ie antibody was also present in nasal wash specimens in high frequency. Lin ear B cell epitope mapping showed that serum antibodies recognized epitopes located in structurally variable regions of Sic and the amino terminal hyp ervariable region of the M1 protein. Phage display analyses confirmed that the polymorphic regions of Sic are primary targets of host antibodies. Thes e results support the hypothesis that selection of Sic variants occurs on m ucosal surfaces by a mechanism that involves acquired host antibody.