Neutralizing murine monoclonal anti-interleukin-10 antibodies enhance binding of antibodies against a different epitope.
Fifteen murine hybridoma lines that produce monoclonal antibodies against human interleukin-10 (IL-10), which is one of the most important regulatory cytokines of the immune system, were raised. Twelve of these antibodies, all in the class IgG1/kappa, recognize three groups of epitopes: A, B and C. All antibodies in these groups inhibit binding of antibodies of the same group to IL-10 and none of them inhibit binding of an antibody of another group. Two IgM/kappa antibodies and one IgG1/kappa antibody, with low affinity, have distinct binding properties and cannot be assigned to one of these groups. Antibodies from all three epitope groups inhibit the biological activity of IL-10. The three antibodies of group A neutralize IL-10 in an approximately equimolar ratio, at concentrations as low as 10 pM. In addition to their high neutralizing capacity, antibodies of group A enhance the binding of antibodies of group C to IL-10. The on-rate of binding of the two antibodies CB/RS/10 and 11 (group C) increased five- to seven-fold, when one of the antibodies CB/RS/1, 2 or 14 (group A) is bound to IL-10.
Sabat
R
R
Department of Immunology, Humboldt University Berlin Medical School (Charité), Germany.
Seifert
M
M
Volk
H D
HD
Glaser
R W
RW
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000494:pharmacology*; D001667:Binding, Competitive / Q000276:immunology; D004357:Drug Synergism; D018604:Epitope Mapping / Q000379:methods*; D000939:Epitopes / Q000276:immunology*; D005260:Female; D006801:Humans; D016753:Interleukin-10 / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D015854:Up-Regulation / Q000276:immunology*
D000276:Adjuvants, Immunologic; D000911:Antibodies, Monoclonal; D000939:Epitopes; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10