Human IgA1 blockade of IgG-initiated lysis of Neisseria meningitidis is a function of antigen-binding fragment binding to the polysaccharide capsule

• Published in: The Journal of immunology (1950) Vol. 147; no. 6; pp. 1962 - 1967
• Main Authors: Jarvis, GA, Griffiss, JM
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Am Assoc Immnol 15-09-1991; American Association of Immunologists
• Subjects: Antibodies, Bacterial - immunology; Antibodies, immunoglobulins; Antigens, Bacterial - immunology; Biological and medical sciences; Complement Activation; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Humans; Immunoglobulin A - immunology; Immunoglobulin Fab Fragments - immunology; Immunoglobulin G - immunology; In Vitro Techniques; Molecular immunology; Neisseria meningitidis - immunology; Polysaccharides, Bacterial - immunology; Receptors, Fc - physiology; Structure; Human; Immunoglobulins; Neisseriaceae; IgG; Activation; Complement; Neisseria meningitidis; IgA1; Structure function relationship; Microorganism capsule; Specificity; Lysis; Bacteria; Micrococcales; Inhibition; Mechanism of action; Polysaccharide; Comparative study
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.147.6.1962

We have recently shown that human IgA1 can initiate lysis of group C Neisseria meningitidis via the classical C pathway when bound to specific outer membrane proteins, but that IgA1 can also function as a blocking antibody when bound to the polysaccharide capsule of meningococci. In this report, we further characterized IgA1 blockade by examining the effect of IgA1 on IgG-initiated immune lysis of group C meningococci. We purified IgG and monomeric IgA1 from either convalescent group C meningococcal case sera or tetravalent (A, C, Y, W135) polysaccharide vaccinate sera. In the absence of IgA1, IgG initiated complete lysis (greater than 99%) of strains 118V (C:P3,4:L2,4) 126E (C:P3:L1,8), and 35E (C:P5:L2). Addition of IgA1 to the bactericidal reaction mixture completely blocked the lytic function of IgG. Removal of the Fc portion of IgA1 with either pepsin or IgA1 protease did not affect blockade. Both the F(ab')2 and Fab derivatives of IgA1 blocked lysis quantitatively as well as intact IgA1. The Fc fragment produced by IgA1 protease cleavage neither increased nor decreased Fab-mediated blockade. IgA1 and its Fab and F(ab')2 fragments blocked IgG-initiated lysis via either the classical pathway in factor B-depleted and in properdin-deficient serum, the alternative pathway in MgEGTA-chelated serum, or both pathways combined. Absorption of the IgA1 and IgG with alum-bound group C polysaccharide completely removed blocking and lytic activity, respectively, indicating that both the blocking IgA1 and the lytic IgG were specific for the group C capsule. Blocking by IgA1 was a linear function of the polysaccharide Ag-binding capacity (ABC) ratio of blocking IgA1 to lytic IgG. Complete blockade was observed at an ABC ratio of 5.5. At ABC ratios of 3.3 and 4.4, IgA1 affected significant blockade whether added previous to, concurrent with, or subsequent to sensitization of the organisms with IgG. With the use of a C polysaccharide ELISA, we found that the binding of IgA1 to the group C capsule in the presence of IgG exhibited positive cooperativity and therefore that blockade was independent of the ability of IgA1 to directly compete with IgG for binding to epitopes within the group C capsule. We conclude that IgA1, when bound to the group C polysaccharide capsule, can block IgG-initiated lysis of group C meningococci through either the classical or the alternative pathway before or after the organism is exposed to IgG, and that blockade is an Fc-independent event.