Epitopes of Human Chorionic Gonadotropin and Their Relationship to Immunogenicity and Cross-Reactivity of β-Chain Mutants
Version of Record online: 6 SEP 2011
American Journal of Reproductive Immunology
Volume 40, Issue 3, pages 210–214, September 1998
How to Cite
PORAKISHVILI, N., JACKSON, A.M., de SOUZA, J.B., CHIESA, M. D., ROITT, I.M., DELVES, P.J. and LUND, T. (1998), Epitopes of Human Chorionic Gonadotropin and Their Relationship to Immunogenicity and Cross-Reactivity of β-Chain Mutants. American Journal of Reproductive Immunology, 40: 210–214. doi: 10.1111/j.1600-0897.1998.tb00414.x
- Issue online: 6 SEP 2011
- Version of Record online: 6 SEP 2011
- Accepted March 1, 1998
- human chorionic gonadotropin (hCG);
- luteinizing hormone (LH);
PROBLEM: Human chorionic gonadotropin (hCG) is a placental glycoprotein hormone, a heterodimeric molecule, consisting of α and β chains. It induces the synthesis of progesterone, which is essential for the maintenance of the fertilized egg. Antibodies directed against hCG can, therefore, prevent pregnancy and serve as a vaccine. hCG belongs to the glycoprotein hormone family and shares the α chain with the other members. The β chain is a hormone-specific subunit that is unique to hCG, but still possesses 85% amino acid homology with the β chain of luteinizing hormone (LH), which means that prolonged immunization with hCG produces antibodies that cross-react with LH.
METHOD OF STUDY: We have taken an approach involving the mutation of βhCG to eliminate cross-reactive epitopes without affecting the natural folding of the polypeptide chain and thus the unique βhCG-specific epitopes.
RESULTS: Several mutants have been constructed that have maintained the binding to hCG-specific monoclonal antibodies (mAbs) but have lost the ability to bind to a panel of LH cross-reactive mAbs. To investigate the immunogenicity of selected mutants, mice were immunized with expression plasmid DNA, containing the gene for wild-type βhCG and two mutants: mutant 3, with four amino acid substitutions (68 ArgGlu; 74 ArgSer; 75 GlyHis; 79 ValHis), and mutant 7, with a single amino acid substitution (68 ArgGlu).
CONCLUSIONS: Athough both mutants were able to elicit antibody responses in at least some animals, the levels were less than those seen with the wild-type βhCG DNA, and there seems still to be a residual cross-reacitivity with LH. Attempts to improve the immunogenicity of the mutants and to further modify the sequence to remove the cross-reacitivty are currently underway.