Immuno-receptors: from recognition to signaling and function

Abstract

The vertebrate adaptive immune response is initiated by specific recognition of antigens. This is carried out by molecules, soluble or cell surface receptors that are members of the Multichain Immune Recognition Receptors (MIRR) group of proteins. The soluble arm of the response is based on antibodies. Kinetic analysis of antibody-antigenic epitope interactions pioneered insights into the complexity underlying the capacity of relatively limited repertoires of antibodies to recognize an essentially unlimited range of epitopes by employing conformational diversity of a given single sequence. The arm responsible for recognition of cellular targets involves a considerably more elaborate process, predominantly of antigen-derived peptides presented bound to molecules encoded by the major histocompatibility complex (MHC). This remarkable cellular recognition process performed by T-cell receptors requires earlier steps of peptide presentation and involves interactions of the receptor sites with the array of its MHC-peptide composite ligand. In both cases, antigen recognition needs to be followed by its coupling, by biochemical cascades, to different specific responses, namely activation of effector functions. The parameters required for coupling to functional responses are still a focus of intense research. In solution, antigen-antibody aggregation is one established activation process. Those required for coupling antigen recognition to cell activation, whether by Fc receptor bound antibodies or by the B-cell antigen receptor, are also still subject to active research efforts. Though activation by immune-receptors requires antigen recognition, considerable differences could exist among the requirements set by distinct cell types. Moreover, antigen binding requiring intercellular interactions introduces additional complexity.

Keywords: Antibody; Antigenic epitope; Chemical relaxation; Kinetics.