ACTIVATION OF EFFECTOR FUNCTIONS BY IMMUNE-COMPLEXES OF MOUSE IGG2A WITH ISOTYPE-SPECIFIC AUTOANTIBODIES

Citation
E. Rajnavolgyi et al., ACTIVATION OF EFFECTOR FUNCTIONS BY IMMUNE-COMPLEXES OF MOUSE IGG2A WITH ISOTYPE-SPECIFIC AUTOANTIBODIES, Immunology, 84(4), 1995, pp. 645-652
Citations number
52
Categorie Soggetti
Immunology
Journal title
ISSN journal
00192805
Volume
84
Issue
4
Year of publication
1995
Pages
645 - 652
Database
ISI
SICI code
0019-2805(1995)84:4<645:AOEFBI>2.0.ZU;2-1
Abstract
Analysis of five monoclonal autoantibodies, rheumatoid factors produce d by hybridomas generated from spleen cells of BALB/c mice repeatedly infected with A/PR/8/34 human influenza A virus, revealed that they re cognized distinct but spatially related epitopes. The differing isoall otypic specificity of the IgM and IgA monoclonal antibodies correlated with the presence of Ile258 and Ala305, respectively. Although these data suggest that the epitopes recognized are within the CH2 domain, a ll antibodies failed to inhibit Ige antigen reactivity with Staphylaco ccus aureas protein A (SpA), Clq, mouse C3, human Fc gamma RI or mouse Fc gamma RII, activities known to be predominantly determined by CH2 domain structures. Reactivity of the IgA antibody, Z34, with IgG2b all owed further specificity studies using a panel of 26 mutant IgG2b prot eins, each having single amino acid replacements over the surface of t he CH2 domain. The only substitution that affected Z34 reactivity was Asn/Ala297, which destroyed the glycosylation sequon, resulting in sec retion of an aglycosylated IgG molecule. The epitope recognized by Z34 therefore seems to be located outside of the Fc-IR and Clq binding si tes, but to be dependent on the presence of carbohydrate for expressio n. In contrast to the binding studies, complement activation by aggreg ated IgG2a, through classical or alternative pathways, was inhibited b y the presence of autoantibodies. The functional significance of isoty pe-specific autoantibody in immune regulation is discussed.