This research project intends to investigate at the biological, biochemical, and molecular genetic levels the basic regulatory mechanism of the immune system involving interleukin-4 (IL-4), and the mechanism by which IL-4 triggers cells to proliferate and/or differentiate into functionally mature cells. The scientific interests will be principally focused on biochemical properties of the receptor specific for IL-4, and the mechanism of receptor expression in cell proliferation and/or differentiation. Previously, we have succeeded in developing a quantitative receptor binding assay for IL-4, and have identified homogeneous mouse cell lines which express good quantities of IL-4 receptor proteins. In the first aim, therefore, we will employ these tools to 1) develop monoclonal and polyclonal antibodies specific for murine IL-4 receptor proteins; 2) purify and analyze biochemically these receptor proteins, including limited amino acid sequencing; and 3) clone the corresponding cDNA for the IL-4 receptor. Specific binding of IL-4 to its cell surface receptor(s) is the initial event in generating its biological activity. Our recent work on IL-4 receptor expression indicate that the number of cell surface IL-4 receptors is increased (i.e., up-regulated) following exposure of receptor-bearing cells to various activation signals, including IL-4 itself. Upon successful completion of SPECIFIC AIM 1, we will have available both polyclonal and monoclonal anti-IL- 4 receptor antibodies and a cDNA probe for the IL-4 receptor to use for the second aim. These tools will thus enable us to: 1) examine and compare IL-4 receptor expression on various target cells, including constituents of normal hematopoietic cell populations and 2) define mechanisms of induction of receptor expression by IL-4. The biological, biochemical and molecular analyses of the mechanism by which IL-4 exerts its function will add important information for our comprehensive understanding of the immune system. Ultimately, this study may constitute the basis for rational therapeutic approaches to immunologically-mediated disease processes.
| Marcelletti, J F; Ohara, J; Katz, D H (1991) Collagen-induced arthritis in mice. Relationship of collagen-specific and total IgE synthesis to disease. J Immunol 147:4185-91 |
| Suzuki, H; Chung, F Z; Palmer, E et al. (1991) Gene mapping of mouse IL-4 receptor: the loci of interleukin 4 (IL-4) receptor gene and lymphocyte function associated antigen 1 (LFA-1) gene are closely linked on chromosome 7. Immunogenetics 34:252-6 |
