Production, characterization and immunoregulatory activity of anti-idiotypic antibodies in the herpes simplex virus system

Anti-idiotypic antibodies with specificities for herpes simplex virus type 1 (HSV-1) monoclonal antibodies were prepared in rabbits. One, anti-id D, reacted specifically with a monoclonal antibody specific for glycoprotein D (gD) of HSV-1 (MoAb D4.2) and could inhibit its binding to gD, demonstrated by ELISA. The other, anti-id C, although prepared against a monoclonal antibody specific for glycoprotein C (gC) of HSV-1 (MoAb D4.1) reacted with MoAb D4.1, MoAb D4.2, and a monoclonal antibody specific for glycoprotein B of HSV-1 (MoAb D4.8). Furthermore, it could inhibit the binding of each monoclonal to its complementary protein epitope. Thus, anti-id C defined a crossreactive idiotope shared by MoAb D4.1, MoAb D4.2, and MoAb D4.8. Spleen cells from mice primed in vivo with either anti-id D or anti-id C underwent specific proliferation in vitro in response to HSV-1 antigens. Subsequently, intraperitoneally immunized mice were tested for a HSV-1 delayed type hypersensitivity (DTH) response. Neither anti-id C nor anti-id D sensitized mice for a HSV-1 DTH response, conversely, anti-id C immune mice were tolerized for a HSV-1 DTH response. This tolerization could be adoptively transferred to naive X-irradiated mice by splenic T cells, and was specific for HSV-1 DTH. Thus, DTH tolerized mice responded to vaccinia and HSV-2 challenge, while remaining tolerized for HSV-1 DTH. In addition, these animals demonstrated a form of split tolerance such that HSV antibody, CTL, and lymphoproliferative responses were detected in vitro. Thus, anti-id C induced a T cell population capable of specifically iv suppressing the HSV-1 DTH response, mimicking the activity of intraperitoneal and intravenous immunization with HSV-l.