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
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.