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Identification of a heterodimer-specific epitope present in human chorionic gonadotrophin (hCG) using a monoclonal antibody that can distinguish between hCG and human LH

Gadkari, RA and Roy, S and Rekha, N and Srinivasan, N and Dighe, RR (2005) Identification of a heterodimer-specific epitope present in human chorionic gonadotrophin (hCG) using a monoclonal antibody that can distinguish between hCG and human LH. In: Journal of Molecular Endocrinology, 34 (3). pp. 879-887.

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Abstract

Human chorionic gonadotrophin (hCG) is secreted during early pregnancy and is required for implantation and maintenance of the pregnancy. Active or passive immunoneutralization of hCG results in termination of pregnancy and this forms the basis of the hCG-based female contraceptive vaccine. However, the $\beta$ subunit of hCG possesses 85% sequence homology with the first 114 amino acids of the $\beta$ subunit of pituitary human LH (hLH), which is required for ovulation and maintenance of the corpus luteum function during the menstrual cycle. Immunization against hCG or its $\beta$ subunit leads to generation of antibodies that can neutralize hLH due to many shared epitopes and hence may cause abnormal menstrual cycles. Therefore, it is essential to identify epitopes that are different in the two hormones. In the present study, we report a monoclonal antibody (MAb) specific for hCG that shows no binding to the isolated subunits. Interestingly, the MAb also does not bind hLH at all. The epitope mapping analysis revealed that this antibody recognizes a unique discontinuous epitope present only in the heterodimeric hCG and is distinct from the unique C-terminal extension of hCG $\beta$ that is absent in hLH $\beta$. The MAb, either as IgG or its recombinant single-chain variable region fragment, inhibited the response to hCG, but not to hLH. Thus, the epitope recognized by this MAb is an ideal candidate antigen for immunocontraception.

Item Type: Journal Article
Additional Information: The Copyright belongs to Society for Endocrinology.
Department/Centre: Division of Biological Sciences > Molecular Biophysics Unit
Division of Biological Sciences > Molecular Reproduction, Development & Genetics (formed by the merger of DBGL and CRBME)
Date Deposited: 01 Mar 2006
Last Modified: 27 Aug 2008 11:46
URI: http://eprints.iisc.ernet.in/id/eprint/5641

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