Functional analysis of IgA antibodies specific for a conserved epitope within the M protein of group A streptococci from Australian Aboriginal endemic communities

The mucosa is one of the initial sites of group A streptococcal (GAS) infec tion and salivary IgA (slgA) is thought to be critical to immunity. However , the target epitopes of slgA and the function of slgA in GAS immunity, in particular the role of accessory cells and complement, is largely unknown. We studied the aquisition and the function of slgA specific for a conserved region epitope, p145 (sequence: LRRDLDASREAKKQVEKALE) of the M protein. Pe ptide 145-specific slgA is highly prevalent within an Aboriginal population living in an area endemic for GAS and acquisition of p145-specific slgA in creases with age, consistent with a role for such antibodies in immunity to GAS. Human slgA and IgG specific for p145 were affinity purified and shown to opsonize M5 GAS in vitro. Opsonization could be specifically inhibited by the addition of free p145 to the antibodies during assay. Opsonization o f GAS was totally dependent on the presence of both complement and polymorp honuclear leukocytes, and, moreover, affinity-purified p145-specific slgA w as shown to fix complement in the presence of M5 GAS. These data show that mucosal IgA to this conserved region peptide within the M protein has an im portant role in human immunity against GAS and may be useful in a broad-bas ed cross-protective anti-streptococcal vaccine.