Anti-idiotype antibodies prevent antibody binding to mouse sperm and antibody-mediated inhibition of fertilization.
Antibodies to components of sperm can interfere with sperm function and prevent fertilization by blocking specific steps of gamete interaction. It can be proposed that anti-idiotype antibodies (anti-Ids) that recognize determinants located close to or within the antigen-binding site of an anti-sperm antibody could block antibody binding to sperm antigen and antibody-mediated inhibition of fertilization. To test this hypothesis, rabbit polyclonal antibodies to idiotypic determinants of the monoclonal anti-sperm antibody M42.15 were developed and characterized. Previous studies demonstrated that M42.15 monoclonal antibody (mAb) inhibits fertilization in vitro and in vivo by inhibiting sperm-zona pellucida interaction. Anti-idiotype antibodies to M42.15 mAb (anti-Id M42) were isolated by affinity chromatography on immobilized M42.15 mAb. Binding specificity of anti-Id M42.15 was demonstrated in a solid-phase radioimmune binding assay and by specific immunoprecipitation of soluble M42.15 mAb. Anti-Id M42 competitively inhibited M42.15 mAb, but not P220.2 mAb, binding to mouse sperm, confirming that the anti-Id preparation contained antibodies directed against idiotopes within or adjacent to the antigen-binding site of the mAb. At equimolar concentrations, anti-Id M42 inhibited binding of 125I-labeled M42.15 mAb to sperm by greater than 80%. These results showed that anti-Id M42 efficiently blocked antibody binding to sperm and suggested that anti-Id M42 could be used to neutralize the anti-fertility activity of the M42.15 mAb. When tested in in vitro fertilization assays, anti-Id M42, but not rabbit immunoglobulin, prevented M42.15 mAb-induced inhibition of fertilization. Together, these results show that the inhibitory activity of anti-sperm antibodies capable of interfering with gamete interaction can be neutralized by anti-Id that recognize determinants close to the antigen-combining site of the anti-sperm antibody.
Carron
C P
CP
Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, North Carolina 27710.
Mathias
A
A
Saling
P M
PM
D000818:Animals; D000906:Antibodies / Q000276:immunology* / Q000378:metabolism / Q000502:physiology; D000939:Epitopes / Q000276:immunology; D005260:Female; D005306:Fertilization / Q000187:drug effects*; D007130:Immunoglobulin Idiotypes / Q000276:immunology* / Q000378:metabolism; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D013084:Sperm-Ovum Interactions / Q000187:drug effects; D013094:Spermatozoa / Q000276:immunology* / Q000378:metabolism
D000906:Antibodies; D000939:Epitopes; D007130:Immunoglobulin Idiotypes