On Origin and Evolution of the Antibody Molecule

Abstract

The vertebrate immune system provides a powerful defense because of the ability to potentially recognize an unlimited number of pathogens. The antibody molecule, also termed immunoglobulin (Ig) is one of the major mediators of the immune response. It is built up from two types of Ig domains: the variable domain, which provides the capability to recognize and bind a potentially infinite range of foreign substances, and the constant domains, which exert the effector functions. In the last 20 years, advances in our understanding of the molecular mechanisms and structural features of antibody in mammals and in a variety of other organisms have uncovered the underlying principles and complexity of this fundamental molecule. One notable evolutionary topic is the origin and evolution of antibody. Many aspects have been clearly stated, but some others remain limited or obscure. By considering a wide range of prokaryotic and eukaryotic organisms through a literature survey about the topic, we have provided an integrated view of the emergence of antibodies in evolution and underlined the very ancient origins.

Principles and Current Clinical Landscape of Multispecific Antibodies against Cancer

“…Basic building block for both chain types is the “Ig domain”, aka “Ig fold”, which is a sandwich-like structure formed by two sheets of 7–9 antiparallel β-strands arranged with a Greek-key topology [ 26 ]. This basic motif appears to be conserved throughout the evolution of life, presumably because its efficient and compact folding provides a suitable substrate for numerous essential recognition, binding and adhesion processes carried out by members of the large Ig protein superfamily [ 1 ]. Each human antibody heavy chain consists of four domains, three constant ones (termed C H 1, C H 2 and C H 3) and one variable (V H ), while the light chains consist of one constant (C L ) and one variable domain (V L ) each.…”

“…The tortuous, 2.5 billion-years-long path from immunoglobulin (Ig)-like domains of archaeal flagellins to the antibodies (Ab) of jawed vertebrates is one of the most intriguing discoveries in evolutionary biology [ 1 , 2 , 3 ]. Equally impressive are the accomplishments of modern genetic engineering, whose further variation of basic Ig building blocks could produce over 40 different molecular formats of therapeutic antibodies during the last two decades [ 4 ].…”

Comparative Analysis of the pIgR Gene from the Antarctic Teleost Trematomus bernacchii Revealed Distinctive Features of Cold Adapted Notothenioidei

“…The polymeric immunoglobulin receptor (pIgR) emerged early in evolution with teleost fish [1] and coevolved with mucosal Ig isotypes, ensuring a mucosal protection [2]. It has a conserved structure, consisting of an extracellular region composed of varying numbers of IgV domains, increasing across the evolutionary scale [3], a transmembrane region and a cytoplasmic tail [4]. In mammals, pIgR has five IgV domains (D1-D5), except for the bovine and rabbit IgRs having three (D1, D4, and D5) of the five domains, derived from alternative splicing [5,6].…”

Topological and Structural Plasticity of the Single Ig Fold and the Double Ig Fold Present in CD19

“…The protodomain (half-domain) hypothesis tends to support the IgV domain as the ancestral form in a divergent evolution scenario. Arguments on the origin of the Ig domain have been partially reviewed in the literature [ 26 , 32 ]. In the following, we analyze the structural and topological domains in light of the Ig fold pseudosymmetry and a possible parallel evolution of these topological domains.…”