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Human sperm and blood cells were cocultured in vitro to determine whether specific interactions occur between gametes and blood cells. Evidence for cell type-specific sperm binding and penetration of lymphocytes is presented together with findings that suggest that either or both events involve major histocompatibility complex-encoded class II molecules on lymphocytes and a sperm ligand that is immunoreactive with antibodies to T-cell surface antigen T4. Involvement of HLA-DR is suggested by the pattern of sperm interactions with HLA-DR-positive and -negative cells and by inhibition of sperm binding to HLA-DR-positive cells by a monoclonal antibody that identifies a nonpolymorphic determinant on the HLA-DR molecule. That the complementary sperm ligand may be a T4-like structure is suggested by specific inhibition of sperm-lymphocyte binding with monoclonal antibodies OKT4 and OKT4A. The results are discussed in terms of possible roles for immunoglobulin-related structures in human fertilization and in the sexual transmission of the acquired immunodeficiency syndrome.

Lymphocyte major histocompatibility complex-encoded class II structures may act as sperm receptors.