Antibodies binding to discrete segments of CϵmX of mIgE on B lymphocytes (P6004)

Abstract

Abstract CϵmX is a discrete domain of 52 a.a. residues, located between the CH4 domain and the C-terminal membrane anchor peptide of the ϵ heavy chain of membrane-bound IgE (mIgE) on human B cells. Among the monoclonal antibodies (mAbs) prepared for their ability to bind to CϵmX fragments or CϵmX-containing recombinant proteins in ELISA, those that can bind to native mIgE on B cells can cause ADCC, apoptosis, and other cytolytic mechanisms on the B cells and are potential useful for controlling IgE production for treating allergic diseases. The CϵmX-specific mAbs prepared previously appear to recognize discrete and overlapping peptide segments of CϵmX. A linear peptide epitope of an antibody is defined by a contiguous peptide segment of minimal stretch that confers maximum binding by the antibody. In some instances, while the peptide epitopes recognized by two mAbs may be adjacent to each other and overlap, the two mAbs do not bind to the adjacent epitopes by a substantial degree. This can be illustrated by the pair of humanized mAbs, h4B12 and h47H4. The mAb h4B12 binds to peptide P1-15 (GLAGGSAQSQRAPDR) and h47H4 binds to peptide P7-18 (AQSQRAPDRVLC). Although the two epitopes share a segment AQSQRAPDR, the mAb h4B12 does not bind to P7-18, and h47H4 does not bind to P1-15. A related presentation from our group (Hsing-Mao Chu et al.) will also reveal that the shared peptide segment AQSQRAPDR has two markedly different conformations when it is associated with h4B12 or with h47H4.