Antibodies as molecular mimics of biomolecules: roles in understanding physiological functions and mechanisms

Abstract

Physiologists have routinely used understanding of the immune system to generate antibodies against regulatory molecules, growth factors, plasma membrane receptors, and other mammalian molecules in the development of analytical tools and assays. In taking this notion further, antibodies have been used in vivo to modulate physiological systems and to improve our understanding of their molecular interactions. To develop antibodies with physiological activity (efficacy), physiologists have worked with immunologists in developing interdisciplinary insights, requiring basic knowledge of immune system function in designing strategies to generate antibodies that interact with endogenous molecules of physiological interest, in vivo. Antibodies in different physiological systems have been shown to enhance or inhibit endogenous molecular functions. Two approaches have been used: passive and active immunization. Antibodies in these contexts have provided tools to develop further insights into molecular physiological mechanisms. Perhaps surprisingly, enhancing antibodies have been developed against a diverse set of target molecules including several members of the growth hormone/insulin-like growth factor-I axes and those of the beta(2)-adrenoceptor axis. Antibodies that inhibit the actions of somatostatin have also been developed. A further novel approach has been the development of antibodies that interact with adipose cells in vivo. These have the potential to be used in therapeutic antiobesity approaches. Antibodies with efficacy in vivo have provided new insights into molecular physiological mechanisms, enhancing our understanding of these complex processes.

Effects of active immunization against the recombinant second extracellular loop of sheep β₂-adrenoceptor on growth and blood biochemical parameters of female rats

“…First, the antibodies might behave similarly to the conventional agonists, by causing a conformational change in the receptor protein upon binding. This proposed conformational change may then lead to receptor activation (Hill et al, 2008). Second, the binding sites on the receptor for the antibodies and conventional ligands would be different.…”

“…Second, the binding sites on the receptor for the antibodies and conventional ligands would be different. Sterically, antibodies would be precluded from binding to the conventional ligand-binding sites deep within the receptor (Hill et al, 2008). Because the molecular mass of conventional agonists is ~1/1,000 th that of IgG.…”