The major hormone-specific discontinuous epitopes on human chorionic gonadotrophin

Abstract

The hormone human chorionic gonadotrophin (hCG) shows extensive sequence homology with LH. Thus, many of the antigenic epitopes on hCG are shared with LH, leading to immunological cross-reaction between these two hormones. Anti-fertility and anti-cancer vaccines based upon hCG should ideally target only the hCG-specific epitopes. The hCG-unique linear epitopes located in the C-terminal peptide of the hCG beta-chain are well characterised. In contrast, the hCG-specific discontinuous epitopes, termed beta1, beta6 and beta7, have remained poorly defined. By generating hCG beta-chain molecules containing single amino acid substitutions we have identified R10, N13, R60 and Q89 as being important in the formation of the beta1 epitope, with R60 providing a particularly dominant residue. We also show that the amino acid residue Q89 contributes to the beta7 epitope, whilst D61 plays a role in both the beta6 and beta7 epitopes.