The objective of this study is to define the role of a new immunoglobulin family of mast cell and macrophage molecules, the gp49 family, by demonstrating their interactions with helper T cells and identifying, characterizing and cloning the T cell counterligand. The candidate will demonstrate direct interaction of gp49 with helper T cells by generating both monoclonal antibodies against gp49 epitopes and soluble chimeric proteins containing the extracellular domains of gp49. She will use the antibodies and chimeric proteins to block the interactions. Once a gp49-mediated mast cell and T cell interaction is demonstrated convincingly, the candidate will generate monoclonal antibodies against the T cell counterligand in order to conduct blocking and immunoprecipitation studies. If these studies define a novel counterligand, isolation, characterization, and cloning of the epitope(s) will be undertaken. Because mast cells and T cells possess common adhesion receptors and home to the same tissues, the applicant hypothesizes that T cell - mast cell interactions may be a critical component of cognate and/or noncognate responses that affect allergic and inflammatory diseases.
| Castells, M C; Klickstein, L B; Hassani, K et al. (2001) gp49B1-alpha(v)beta3 interaction inhibits antigen-induced mast cell activation. Nat Immunol 2:436-42 |
