Immunological Properties of the β-Subunit of Human Chorionic Gonadotropin. I. Effect of Chemical and Enzymatic Modifications*

Abstract

The .beta.-subunit of hCG [human chorionic gonadotropin] (hCG.beta.) displays immunological crossreactivity with human LH [lutropin] (hLH). The effect of chemical and enzymatic modifications on the immunological behavior of hCG.beta. was studied, particularly on its crossreactivity with hLH, with a view to obtaining a highly hCG-specific antigen. hCG.beta. was modified in both the carbohydrate and protein parts of the molecule. The carbohydrate part was modified enzymatically by sequential cleavage of monosaccharides by specific glycosidases, and the protein portion was modified chemically in the amino and carboxyl groups and in the cystinyl, tyrosyl, histidyl and arginyl residues. These derivatives were immunological evaluated by RIA [radioimmunoassay]; their hCG.beta. activities were measured in the [125I]hCG.beta.-anti-hCG.beta. system and the hLH crossreactivity in the [125I]hLH-anti-hLH system. The carbohydrate apparently does not play a significant role in the immunological activity of hCG.beta.. The antigenic determinants of hCG.beta. reside primarily in the polypeptide chain and are conformational rather than sequential in nature. hCG.beta. has 2 types of antigenic determinants, those which are unique to hCG and those which are common to both hCG and hLH. It is possible to destroy preferentially 1 or the other type of determinants. The controlled reduction and alkylation of hCG.beta. yielded derivatives which retain significant immunological activity in the hCG.beta. syste, but have no or reduced crossreactivity in the hLH system. These derivatives are much more specific antigens than hCG.beta. and are potentially important for the development of a specific RIA for hCG and possibly for use as contraceptive agents.