POSTINFECTIOUS HUMAN SERUM ANTIBODIES INHIBIT IGA1 PROTEINASES BY INTERACTION WITH THE CLEAVAGE SITE-SPECIFICITY DETERMINANT

Bacterial pathogens of the genera Neisseria and Haemophilus secrete Ig A1 proteinases which cleave human IgA1 in the heavy chain hinge region . The exact peptide bond cleaved is strain-dependent, but remains inva riant despite repeated subculture. Haemophilus influenzae and Neisseri a meningitidis produce proteinases of two cleavage site specificities (type 1 and type 2). We examined serial acute and convalescent sera fr om patients recovering from meningitis due to N. meningitidis or H. in fluenzae, and found a significant rise in serum titer of inhibitory an tibodies against these enzymes. In each case the proteinase from the i nfecting organism was more susceptible to inhibition than were protein ases from that genus that had different cleavage specificity. Inhibiti on of sixteen type 1-type 2 hybrid H. influenzae IgA1 proteinases reve aled complete concordance between inhibitory titer and cleavage site s pecificity. Inhibition of hybrid proteinases differing in a 123 amino acid segment known to determine cleavage site specificity (termed the CSD) further localized the site of antibody action to this site. These results from a limited number of patients with natural infections sug gest that inhibiting antibody recognizes epitopes within the CSD. Alte rnatively, antibody may bind to epitopes outside the CSD and inhibit v ia steric hindrance.