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.

The Emerging Roles of Human Leukocyte Antigen-F in Immune Modulation and Viral Infection

“…Human leukocyte antigen (HLA) class I antigens have multiple important functions in immune regulation. The functions of HLA class I antigens are involved in presenting antigens to T cells and serving as ligands for a panel of immune receptors expressed on natural killer (NK) cells, T cells, and myeloid cells (1, 2). The HLA class I family can be further grouped as the classical (HLA-Ia) and nonclassical antigens (HLA-Ib).…”

Role of FcγRIII in the nasal cavity of BALB/c mice in the primary amebic meningoencephalitis protection model

“…The activation of FcγRIII mediates among other responses the release of NETs, due to the activation pathways initiated by Hck and Syk (Futosi et al 2013;Pecht 2018;Rosales 2007;Suzuki et al 2000). The cascade triggers the phosphorylation of extracellular signal-regulated kinase (ERK), which also contributes to the activation of NADPH oxidase, followed by phosphorylation of the nuclear factor Elk-1, resulting in NETosis (Alemán et al 2016;Behnen et al 2014;García-García et al 2009;Papayannopoulos et al 2010).…”

Membrane Organization and Physical Regulation of Lymphocyte Antigen Receptors: A Biophysicist’s Perspective

“…Receptor diversity encoded in the CDR is responsible for its specificity and affinity for the antigen (Murphy 2016;Pecht 2018). Since antigen receptors are deprived of cytoplasmic domains, a long-standing question was to understand how antigen binding is triggering downstream intracellular signal, i.e.…”