T CELL REGULATION OF B CELL IDIOTYPE EXPRESSION

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.