The Journal of Immunology, Vol 147, Issue 6 1962-1967, Copyright © 1991 by American Association of Immunologists

ARTICLES

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

GA Jarvis and JM Griffiss
Department of Laboratory Medicine, University of California, San Francisco.

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.

This article has been cited by other articles:

				G. Norheim, A. Aseffa, M. A. Yassin, G. Mengistu, A. Kassu, D. Fikremariam, W. Tamire, Y. Merid, E. A. Hoiby, D. A. Caugant, et al. Serum Antibody Responses in Ethiopian Meningitis Patients Infected with Neisseria meningitidis Serogroup A Sequence Type 7 Clin. Vaccine Immunol., April 1, 2007; 14(4): 451 - 463. [Abstract] [Full Text] [PDF]

				I. R. Henderson, F. Navarro-Garcia, M. Desvaux, R. C. Fernandez, and D. Ala'Aldeen Type V Protein Secretion Pathway: the Autotransporter Story Microbiol. Mol. Biol. Rev., December 1, 2004; 68(4): 692 - 744. [Abstract] [Full Text] [PDF]

				J. Southern, S. Deane, L. Ashton, R. Borrow, D. Goldblatt, N. Andrews, P. Balmer, R. Morris, J. S. Kroll, and E. Miller Effects of Prior Polysaccharide Vaccination on Magnitude, Duration, and Quality of Immune Responses to and Safety Profile of a Meningococcal Serogroup C Tetanus Toxoid Conjugate Vaccination in Adults Clin. Vaccine Immunol., November 1, 2004; 11(6): 1100 - 1104. [Abstract] [Full Text] [PDF]

				G. B. Pier, D. Boyer, M. Preston, F. T. Coleman, N. Llosa, S. Mueschenborn-Koglin, C. Theilacker, H. Goldenberg, J. Uchin, G. P. Priebe, et al. Human Monoclonal Antibodies to Pseudomonas aeruginosa Alginate That Protect against Infection by Both Mucoid and Nonmucoid Strains J. Immunol., November 1, 2004; 173(9): 5671 - 5678. [Abstract] [Full Text] [PDF]

				T. Burns, Z. Zhong, M. Steinitz, and L.-a. Pirofski Modulation of Polymorphonuclear Cell Interleukin-8 Secretion by Human Monoclonal Antibodies to Type 8 Pneumococcal Capsular Polysaccharide Infect. Immun., December 1, 2003; 71(12): 6775 - 6783. [Abstract] [Full Text] [PDF]

				S. R. Hedges, M. S. Mayo, L. Kallman, J. Mestecky, E. W. Hook III, and M. W. Russell Evaluation of Immunoglobulin A1 (IgA1) Protease and IgA1 Protease-Inhibitory Activity in Human Female Genital Infection with Neisseria gonorrhoeae Infect. Immun., December 1, 1998; 66(12): 5826 - 5832. [Abstract] [Full Text] [PDF]

				B. Haneberg, R. Dalseg, E. Wedege, E. A. Hoiby, I. L. Haugen, F. Oftung, S. R. Andersen, L. M. Nass, A. Aase, T. E. Michaelsen, et al. Intranasal Administration of a Meningococcal Outer Membrane Vesicle Vaccine Induces Persistent Local Mucosal Antibodies and Serum Antibodies with Strong Bactericidal Activity in Humans Infect. Immun., April 1, 1998; 66(4): 1334 - 1341. [Abstract] [Full Text] [PDF]

				T. S. Mattu, R. J. Pleass, A. C. Willis, M. Kilian, M. R. Wormald, A. C. Lellouch, P. M. Rudd, J. M. Woof, and R. A. Dwek The Glycosylation and Structure of Human Serum IgA1, Fab, and Fc Regions and the Role of N-Glycosylation on Fcalpha Receptor Interactions J. Biol. Chem., January 23, 1998; 273(4): 2260 - 2272. [Abstract] [Full Text] [PDF]