Biological Activities Residing in the Fc Region of Immunoglobulin

Abstract

This chapter discusses studies involving lymphocyte activation and immune regulation by peptides derived from IC and Fc fragments of immunoglobulin (Ig). The cellular and subcellular events involved in lymphocyte activation by these biologically active peptides are discussed. There are five major classes of mammalian Ig: IgG, IgM, IgA, IgD, and IgE. The fundamental structure of the Ig molecule consists of two identical light (L) and two identical heavy (H) chains. IgG can be cleaved into smaller fragments by a variety of enzymes other than papain. Pepsin cleaves Ig on the carboxy terminal side of the inter-H chain disulfide bonds, resulting in the formation of a large F (ab')2 fragment. The Fc fragment is degraded by pepsin into heterogeneous peptides. The Fc region of the Ig molecule is involved in a wide variety of biological effector functions that include control of catabolic rate, C fixation, binding to FcR, anaphylaxis, opsonization, placental and gut transfer, and immune regulation. Because the cellular events in lymphocyte activation by Fc fragments and IC appear to be identical, perhaps immunoregulation by these agents occurs via similar pathways. The release of biologically active peptides derived from the Fc fragment of antibody may be part of a potent nonspecific in vivo immunoregulatory network. In addition to the release of Fc region peptides, IC formation also results in C activation with the subsequent release of C fragments (C3a and C5a) that possess immunoregulatory properties.