The primary objective is to understand the basic cellular mechanisms involved in T cell regulation of the expression of the B cell idiotype (Id) repertoire. Multiple T cell regulatory mechanisms appear to be involved in the regulation of idiotype expression in the murine antibody response to phosphorylcholine (PC), a common bacterial antigen. Using monoclonal anti- idiotope antibodies as probes, this project will examine the role of four distinct types of cloned T inducer cells in id regulation; (1) Carrier (KLH)-specific T cells, (2) PC-specific T cells (Id+ T cells), (3) Autoreactive T cells, and (4) Idiotype-reactive (anti-Id) T cells. The initial studies on the cellular mechanisms of Id regulation will focus on; (1) Comparing and combining different T cell clones, (2) Examining the effects of T-derived lymphokines, and (3) Studying the role of differential B cell Ia antigen expression. If Id+ and/or anti-Id T cells can be isolated and propagated, serologic and biochemical identification of T and B cell recognition structures which """"""""mimic"""""""" each other will be attempted. The control of id expression may have special relevance to the pathogenesis of autoimmunity. In the PC system, anti-idiotypic antibodies have been found which cross-react with acetylcholine receptors (AChR), suggesting a link between dysregulation of antibacterial responses and myasthenia gravis. The project will seek to exploit the combined expertise of two laboratories. The principal investigator has considerable experience in T cell cloning while the co-investigator is well known for work on anti-PC idiotype expression. Conventional cellular immunology and tissue culture techniques will be used to clone murine inducer T cells and to measure antibody responses by plaque-forming assays.
