Interaction between streptococcal protein Arp and different molecular forms of human immunoglobulin A

Protein Arp, the IgA-binding protein of the group A Streptococcus, has affinity for the Fc-part of IgA. The binding between protein Arp and several different molecular forms of human IgA was characterized. It was found that protein Arp bound with higher affinity to uncomplexed forms of IgA than to complexed forms (secretory IgA, α 1-antitrypsin-IgA and α 1-microglobulin-IgA). Thus, the affinity constant was 2.0−5.9 × 10 8 M −1 for the binding to monomeric, dimeric, trimeric and quadrimeric IgA, and 4.5−5.0 × 10 7M −1 for binding to the complexed forms. Among the uncomplexed IgA-molecules, the affinity constant was in the same range for J chain-containing forms (dimeric, trimeric and quadrimeric IgA) as for forms without J chain (monomeric and a particular quadrimeric IgA devoid of J chain). Western blotting demonstrated that protein Arp bound exclusively to the α-chain of all IgA-forms. Several lines of evidence pointed to a localization of the binding site to the Cα3-domain. First, protein Arp did not bind to three N-terminal α-chain fragments which lacked a region corresponding to the Cα 3-domain, including that from a four-chain myeloma IgA, naturally occuring in plasma. Second, the binding to dimeric and tri/quadrimeric IgA was partially blocked by an added secretory component, which has been suggested to bind to the Cα2- and Cα3-domains of the α-chain. Finally, α 1-antitrypsin and α 1-microglobulin, in the weakly binding IgA-complexes, have been shown to be linked to the Cα3-domain via the penultimate amino acid residue of the α-chain peptide, supporting the hypothesis of a localization of the binding site of protein Arp to the Cα3-domain.