S. Subramanian et al., Strain-dependent variability in immune response to chicken riboflavin carrier protein in mice with different haplotypes, IMMUNOL INV, 29(4), 2000, pp. 397-409
Active immunization of fertile female mice, rats and sub-human primates wit
h linearized chicken riboflavin carrier protein (RCP) curtailed pregnancy s
uggesting that sequence-specific RCP antibodies interfere with fertilizatio
n/early embryo development. To investigate the genetic basis of variations
in immunogenecity, antibody response to reduced and carboxymethylated RCP (
RCM-RCP) was studied in different strains of mice of independent H-2 haplot
ypes. Among these, AKR (H-2(k)) were low or non-responders. Measurement of
antibody titers in hyperimmune sera showed that among responder strains of
mice, C57BL/6 (H-2(b)) and BALB/c (H-2(d)) generated higher levels of antib
ody compared to mice of SJLJ (H-2(S)). The relative affinities of these ant
ibodies also varied depending upon the strain, with BALB/c mice showing hig
hest affinity. Epitope mapping by pepscan ELISA revealed significant variab
ility in determinant-specific antibody populations, with SJLJ strain lackin
g antibodies to N-terminal half of RCP sequence. However, four immunodomina
nt sequential epitopes (residues 100-107, 134-141, 174-181 and 200-207) com
mon to all the three strains of mice have been identified. Binding to these
regions was not haplotype restricted although there were qualitative diffe
rences in recognition patterns. Present investigations have shown that site
-specific antibodies directed towards any one of the four epitopic regions
comprising of residues 3-24, 64-83, 130-147 and 200-219 in chicken RCP sequ
ence effectively interfered with pregnancy establishment in female BALB/c m
ice. This implies the propensity of RCP antibodies to curtail pregnancy in
the other two responder mouse strains also.