IDENTIFICATION AND CHARACTERIZATION OF AN I-J INTERACTING MOLECULE

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.