IDENTIFICATION AND CHARACTERIZATION OF AN I-J INTERACTING MOLECULE

Date

1987

Authors

ZUPKO, KARIN GAY

Journal Title

Journal ISSN

Volume Title

Publisher

ProQuest Dissertations & Theses

YU Faculty Profile

Abstract

In recent years, immunologists have begun to understand the mechanism of T-helper (Th)-cell activation: T-cell receptors on Th cells, Ia molecules on accessory cells, and foreign antigen interact in a trimolecular complex leading to antigen specific and genetically restricted activation of Th cells. Little is known, however, about the molecular species involved in activation of T suppressor (Ts) cells. Ts cells express I-J determinants on their surface, and anti-I-J antibodies block induction of suppression both in vivo and in vitro, but the molecule(s) interacting with I-J are unknown. Because the mechanism of suppression may be analogous to the mechanism of Th-cell activation, we hoped to identify the molecule(s) interacting with the I-J determinants on murine Ts cells by generating anti-idiotypic antisera. Two antisera were produced in rabbits: one to monoclonal anti-I-J{dollar}\sp{lcub}\rm d{rcub}{dollar} antibody and one to monoclonal anti-I-J{dollar}\sp{lcub}\rm k{rcub}{dollar} antibody.;These anti-idiotypic antisera can block Ts-cell function in a genetically restricted manner in two distinct systems measuring antigen specific suppression. In one system, the antisera block a primary antibody response to a synthetic polymer as evaluated by plaque-forming cell assays. In the second system, which measures a secondary delayed type hypersensitivity response to a hapten, the antisera block Ts{dollar}\sb{lcub}1{rcub}{dollar}, Ts{dollar}\sb{lcub}2{rcub}{dollar}, and Ts{dollar}\sb{lcub}3{rcub}{dollar}-cell induction. The cellular target of the anti-idiotypic antisera appears to be a macrophage as functional activity of the anti-idiotype can be absorbed by a macrophage cell line in a genetically restricted manner. In addition, IJ-IM does not appear to be a conventional class II antigen.;The IJ-IM has been difficult to isolate and analyze biochemically: no protein specifically recognized by anti-idiotypic antisera has been identified by biochemical analysis. It may be that IJ-IM is present in cell extracts in minute quantities. We hope, however, that eventual characterization of this molecule will help to clarify the molecular interactions that induce suppressor cell activity.

Description

Keywords

Immunology.

Citation

Source: Dissertation Abstracts International, Volume: 48-08, Section: B, page: 2256.