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Mol Cell Endocrinol. 2007 Jan 2;260-262:23-32. Epub 2006 Oct 11.

The antigen binding sites of various hCG monoclonal antibodies show homology to different domains of LH receptor.

Author information

1
Molecular Reproduction, Development and Genetics, Indian Institute of Science, Bangalore 560012, India.

Abstract

The common feature of receptors and antibodies against the ligand is that both display very specific, high affinity binding towards the ligand. Therefore, it can be hypothesized that the paratope of antibodies may exhibit homology with distinct domains of the receptor. By locating the hormone epitopes and determining the structure of the paratopes, it should be possible to identify the contact points between the ligand and the receptor. This hypothesis has been tested using hCG monoclonal antibodies (MAbs) recognizing different epitopes and having different effects on hormone binding and response. The beta subunit and heterodimer specific antibodies inhibited both hormone binding and response, while the alpha subunit specific antibodies inhibited response without affecting binding. The single chain fragment variables (ScFvs) produced from these antibodies also retained the properties of the parent antibodies. The amino acid sequences of the ScFvs exhibited homology to different regions of the receptor; the beta subunit specific antibody being homologous to the concave surface of the leucine rich repeats (LRR) of the receptor, particularly the concave surface of the LRRs, while the heterodimer specific antibody showed homology to the hinge region. The alpha subunit specific antibody showed homology to the transmembrane domain of the receptor. The exact locations of the epitopes of the monoclonal antibodies in the hormone molecule have also been identified. The data presented here also support the model of glycoprotein hormone-receptor interaction in which the hormone binds to the extracellular domain through the beta subunit and then the alpha subunit is brought in contact with the transmembrane domain leading to signal transduction.

PMID:
17045394
DOI:
10.1016/j.mce.2006.07.006
[Indexed for MEDLINE]

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