Salivary agglutinin (SAG) is a 2314 amino acids glycoprotein, encoded by the DMBT-1 gene (Deleted in Malignant Brain Tumors-1), and is a member of the scavenger receptor cysteine rich (SRCR) superfamily. It contains 13 highly homologous 109 amino acids SRCR domains that are involved in bacterial binding. SAG in saliva forms complexes with IgA what may be another mode for bacterial binding. Objectives:to characterize the binding of purified SAG to IgA. Methods: binding of SAG to IgA, albumin and lactoferrin was studied in an ELISA. Binding of IgG antibodies to SAG was tested by Western blotting. Results: SAG binds to both serum and secretory IgA, but also to alkaline phosphatase conjugated IgGs from rabbit, goat, swine and mouse, to lactoferrin and to albumin. Binding of IgA to SAG is calcium dependent and is inhibited by 0.5 M KCl suggesting electrostatic interactions are involved in binding. Binding of IgA was destroyed after reduction of SAG, suggesting the protein moiety was involved in binding. To pinpoint further the binding domain for IgA on SAG, a number of consensus-based peptides of the SRCR domains and SRCR interspersed domains were designed and synthesized. Only one of the peptides tested, extending amino acid 18-33 (QGRVEVLYRGSWGTVC) of the 109 amino acid SRCR domain, exhibited IgA binding properties. The same peptide has been demonstrated to be involved in bacterial binding. Conclusions: binding of IgA to SAG is specifically mediated by a peptide sequence on the SRCR domains. This study was supported by the Dutch Research School for Dentistry (IOT).