Characterization of epitopes of seminal plasma antigen stimulating human monoclonal sperm-immobilizing antibodies: a personal review

Abstract

In observations made between 1974 and 1984, 40 of 303 women with unexplained sterility (13.2%) showed positive sperm-immobilizing antibodies. Among many kinds of antibodies to human sperm including sperm coating antigens, the biologically active antibodies, such as sperm-immobilizing agglutinating antibodies and blocking antibodies for fertilization, could be relevant to infertility. Harmless sperm-binding antibodies are present even in the sera and cervical mucus of fertile women. Antigens corresponding to monoclonal antibodies (1C4, 2C6, 2E5), which were generated to human sperm coating antigens and indicated strong sperm-immobilizing activities, seemed to have carbohydrate epitopes. The majority of women with sterility of unknown cause appeared to raise sperm-immobilizing antibodies to carbohydrate epitopes of sperm. The stable human-mouse heterohybridoma H6-3C4 secreting monoclonal antibody (IgM, lambda) with extremely high titres of sperm-immobilizing (SI50, 5000 units) and agglutinating (1:1600) activities was successfully established from peripheral lymphocytes of a sterile woman. The chemical structure of an antigen epitope corresponding to human monoclonal antibody H6-3C4 was found to consist of internally repetitive, unbranched N-acetyllactosamine (blood type i antigen). Ejaculated human sperm appeared to be densely covered with sialyl blood type i antigen and sialyl branched internally repetitive N-acetyllactosamine (sialyl blood type I antigen). The antibody-producing V-H and V-L genes of the human hybridoma H6-3C1 were cloned and preserved to stabilize antibody production. Class-switch variants of heavy chain from mu to gamma (IgG1, lambda) in human Mab H6-3C4 were produced by recombinant DNA technology.