CHARACTERIZATION OF MURINE AND HUMAN IG-D-RECEPTORS ON T

点击翻译按钮获取中文摘要

Previous observations have established the rapid upregulation by oligomeric or cross-linked, but not monomeric, IgD of receptors for IgD (IgD-R) on a large percentage of murine and human peripheral T cells and helper T cell clones. IgD-R on T cells are also induced by stimulation with anti-CD3, IL-2, IL-4, IFN-gamma, and alternate pathway stimulating agents, such as PMA + ionophore. Many of these reagents, except for IL-2 and alternate pathway stimulators, fail to upregulate IgD-R on T cells from aged mice. In view of the immunoaugmenting properties of IgD-R+ T cells in young, but not in aged mice, these IgD-R appear to stabilize/promote T-B cell interaction, particularly with B cells bearing cross-linked surface IgD. Murine and human helper T hybridoma cells also express IgD-R and release soluble binding factors for IgD (IgD-BF) into their supernatants under the influence of IL-2, IL-4 or crosslinked IgD. Murine IgD-R+ receptors are 40kD molecules that can be specifically precipitated by IgD-Sepharose. These molecules, as well as isolated human IgD-R will be purified and subjected to partial amino acid sequencing. The numbers of IgD-R per cell will be quantitated on normal T cells, IgD-treated T cells and T hybridoma cells. Antibodies to the human IgD-R/BF (LTB9) are available and antibodies to the murine IgD-R/BF are being evaluated for specificity. Cloning of the cDNA of the human and murine IgD-R/BF will be approached using available activated T-cell cDNA libraries. Additional studies will concern the fine specificity of both the murine and human IgD-R: In view of recent findings implicating N-glycans on IgD in its binding to the murine IgD-R, the functional role of these glycans will be investigated. Particular attention will be given to the role of carbohydrate determinants on human IgD in its binding to the human T cell IgD-R.