Structural Immunology: Mechanisms of Antigen Recognition

Abstract

The mechanisms of antigen recognition by the immune system have been extensively addressed during past two decades. Ingeniously designed X-ray crystallographic experiments have provided great insights with regard to antigenic specificity and self/non-self discrimination, the hallmark of the adaptive immune system. These studies have also helped shed light on the mechanistic aspects of the immune recognition potential and the molecular events necessary for a successful immune response. Our laboratory has made important contributions in understanding the physiological processes associated with self-nonself discrimination in terms of physico-chemical principles of molecular interactions. Crystallographic approaches were employed in analyzing how immune system reacts when encountered with the antigens that keep changing shape. We have addressed the breakdown in specificity of immune recognition by providing molecular insights into the functional mimicry. The conundrum of a limited antibody repertoire faced with an infinite range of antigens was also addressed demonstrating that while the pluripotency of germline antibodies can be expressed through an ensemble of conformational states, each one of these states was itself capable of recognizing a wide range of antigens through varied juxtapositions.