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

Author

Janet L. Lathey

Date of Award

6-1986

Degree Type

Dissertation

Degree Name

Doctor of Philosophy

Major

Microbiology

Major Professor

Barry T. Rouse

Committee Members

Richard J. Courtney, Stephen J. Kennel, Arthur Brown, Robert N. Moore

Abstract

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.

Recommended Citation

Lathey, Janet L., "Production, characterization and immunoregulatory activity of anti-idiotypic antibodies in the herpes simplex virus system. " PhD diss., University of Tennessee, 1986.
https://trace.tennessee.edu/utk_graddiss/12285