Toshifumi Mikayama

Controversial Issues and Possible Answers on the Antigen-Specific Regulation of the IgE Antibody Response

In the past 10 years, the major approaches for the regulation of the IgE antibody response by many investigators have been focused to isotype-specific suppression of the IgE synthesis. However, another approach to be considered is to suppress the antibody response to the allergens to which the allergic patients are sensitive. In this presentation, we would like to discuss the possibility to regulate the antibody response in antigen-specific manner, and scientific evidence for the presence of such a mechanism.

The crystallographic analysis of glycosylation-inhibiting factor

Publisher Summary Glycosylation-inhibiting factor (GIF) inhibits N-glycosylation of IgE-binding factors. The unglycosylated IgE-binding factor then selectively suppresses IgE synthesis. Further, GIF appears to be a subunit of antigenspecific suppressor T cell factors that facilitate the generation of antigen-specific suppressor T cells. Recent studies indicate that post-translational modification of GIF in suppressor T cells is required for the generation of the biological activity. However, the relationship between GIF bioactivity and the conformational transition of the protein is not known. To understand the mechanisms of GIF functions, this chapter studies the crystal structure of recombinant human GIF. It is apparent that GIF has a novel tertiary structure. The chapter discusses the crystallographic analysis of GIF. The overall structure of GIF trimer is found to be a three-fold-related barrel structure, which is composed of three six-stranded β-sheets on the inside and six α-helices on the outside. Each subunit consists of two β-α-α motifs related by a pseudo-twofold axis. The trimer structure is formed by intermonomer hydrogen bonds and hydrophobic interfaces among β-sheets. There is a 5-A diameter “hole” through the middle of the barrel. The barrel structure of GIF in part resembles “trefoil” cytokines, such as interleukin-1 and fibroblast growth factor.