Epitopes of glycoprotein hormones and their significance for biological functions

The aim of this thesis was to investigate structure-function relationships of glycoprotein hormones, in particular of human chorionic gonadotropin (HCG) and human follicle stimulating hormone (HFSH). In order to identify structures of functional significance, we initially characterized different antigenic determinants and subsequently investigated the biological roles they play. Concerning epitope localization by radio-immuno-assay (RIA) it revealed that all of the 16 epitopes expressed on HCG are localized on its protein-backbone. Glycosylation does not contribute to the immunological properties of this hormone. 7 out of epitopes on the β-subunit of HCG(HCGβ) are expressed by the HCGβ-core molecule whereas antigenic determinants β8 and β9 are localized on the C-terminal peptide (CTP). Parts of 5 antigenic determinants could be defined by means of synthetic peptides corresponding to HCGα- and HCGβ-sequences: The α4-epitope within the sequence α17-22, the α6-epitope within α33-42 and the HCGβ-epitopes β5(β45-52), β8(β135-145) and β9(β108-120). Concerning hormone-receptor-interaction it could be demonstrated that any of the 9 monoclonal antibodies (MCA) directed against epitopes on the surface of HFSH could totally inhibit binding of I125-HFSH to its receptor on rat testis cell membranes. Probing the 16 MCA directed against epitopes on HCG it revealed that 14 could totally inhibit binding of I125-HCG to its receptor but 2 MCA directed against epitopes β8 and β9 failed to immunoneutralize HCG