Induction of anti-progesterone immunity and pregnancy blocking by anti-progesterone anti-idiotypes. Variable efficacy of polyclonal Ab2 antibodies directed against a panel of closely related Ab1 antibodies.
Polyclonal rabbit anti-idiotypes (Ab2) have been raised against three mouse monoclonal antiprogesterone Ab1 antibodies (DB3, 11/32, 11/64) closely related in VH and VL sequences. The anti-idiotypes were characterized for specificity and used to immunize groups of female mice. The latter responded with production of anti-progesterone (Ab3) antibodies, confirming the ability of anti-idiotypes to mimic the immunogenicity of a steroid. The response to one of the anti-idiotypic reagents (anti-DB3-id) was 5-10 times stronger than those to the others, despite close sequence homology between the idiotypes. Moreover, immunization with anti-DB3-id led to a reduction in fertility rate from 90% (control) to 30%, whereas immunization with the other anti-idiotypes was without effect. Sequence and structural comparisons suggest that residues associated with VH CDR3 and VL CDR3 may have a key role in determining the efficiency of anti-idiotypic immunization against progesterone. The variability in outcome of using anti-idiotypic reagents against a defined panel of related antibodies is relevant to the use of anti-idiotypes as surrogate antigens.
Wang
M W
MW
Department of Immunology, AFRC Institute of Animal Physiology and Genetics Research, Babraham, Cambridge, U.K.
Sims
M J
MJ
Symington
P R
PR
Humphreys
A S
AS
Taussig
M J
MJ
D000595:Amino Acid Sequence; D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology*; D000918:Antibody Specificity; D015551:Autoimmunity / Q000276:immunology*; D001483:Base Sequence; D003269:Contraception, Immunologic; D005260:Female; D005298:Fertility / Q000276:immunology; D007143:Immunoglobulin Heavy Chains / Q000276:immunology; D007130:Immunoglobulin Idiotypes / Q000276:immunology; D007147:Immunoglobulin Light Chains / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D011247:Pregnancy; D011374:Progesterone / Q000097:blood / Q000276:immunology*
D000888:Antibodies, Anti-Idiotypic; D007143:Immunoglobulin Heavy Chains; D007130:Immunoglobulin Idiotypes; D007147:Immunoglobulin Light Chains; D011374:Progesterone