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A key question in immunology is whether antigen recognition and Fc receptor (FcR) binding are allosterically linked. This question is also relevant for therapeutic antibody design. Antibody Fab and Fc domains are connected by flexible unstructured hinge region. Fc chains have conserved glycosylation sites at Asn297, with each conjugated to a core heptasaccharide and forming biantennary Fc glycan. The glycans modulate the Fc conformations and functions. It is well known that the antibody Fab and Fc domains and glycan affect antibody activity, but whether these elements act independently or synergistically is still uncertain. We simulated four antibody complexes: free antibody, antigen-bound antibody, FcR-bound antibody, and an antigen-antibody-FcR complex. We found that, in the antibody's "T/Y" conformation, the glycans, and the Fc domain all respond to antigen binding, with the antibody population shifting to two dominant clusters, both with the Fc-receptor binding site open. The simulations reveal that the Fc-glycan-receptor complexes also segregate into two conformational clusters, one corresponding to the antigen-free antibody-FcR baseline binding, and the other with an antigen-enhanced antibody-FcR interaction. Our study confirmed allosteric communications in antibody-antigen recognition and following FcR activation. Even though we observed allosteric communications through the IgG domains, the most important mechanism that we observed is the communication via population shift, stimulated by antigen binding and propagating to influence FcR recognition.
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Adaptive immune recognition is mediated by antigen receptors on B and T cells generated by somatic recombination during lineage development. The high level of diversity resulting from this process pos...
Since the introduction of the yeast display platform, this method has increasingly gained popularity for the discovery and affinity maturation of antibodies and other protein scaffolds intended for an...
Effectors are microbial-derived secreted proteins with an essential function in modulating host immunity during infections. CfAvr4, an effector protein from the tomato pathogen Cladosporium fulvum and...
Complete activation of B cells relies on their capacity to extract tethered antigens from immune synapses by either exerting mechanical forces or promoting their proteolytic degradation through lysoso...
The σ receptor is a poorly understood membrane protein expressed throughout the human body. Ligands targeting the σ receptor are in clinical trials for treatment of Alzheimer's disease, ischemic str...
A pilot study to determine the safety and efficacy of chimeric antigen receptor T cell (autologous T cells transduced with a lentiviral vector expressing chimeric antigen receptor) persona...
Chimeric antigen receptor (CAR)-modified T cells can mediate long-term durable remissions in recurrent or refractory CD19+ B cell malignancies, and are a promising therapy to treat gliobla...
Objectives: The purpose of this study is to evaluate the safety and prognosis of New Cluster of Differentiation Antigen 19-chimeric Antigen Receptor T (nCAR19-T) Cells in the treatment of...
In treatment-resistant depression, electroconvulsive therapy (ECT) has been shown to effectively reduce depressive symptoms, though the underlying neurobiological mechanism is still unclea...
A Study of LCAR-B38M CAR-T Cells, a Chimeric Antigen Receptor T-cell (CAR-T) Therapy Directed Against B-cell Maturation Antigen (BCMA) in Chinese Participants With Relapsed or Refractory Multiple Myeloma
The purpose of this study is to evaluate the efficacy and safety of LCAR-B38M chimeric antigen receptor T (CAR-T) cells.
A secreted protein that associates with TOLL-LIKE RECEPTOR 4 and is essential for receptor recognition of LIPOPOLYSACCHARIDES.
A pattern recognition receptor that interacts with LYMPHOCYTE ANTIGEN 96 and LIPOPOLYSACCHARIDES. It mediates cellular responses to GRAM-NEGATIVE BACTERIA.
Human histocompatibility (HLA) surface antigen encoded by the A locus on chromosome 6. The HLA-A2 antigen is associated with recognition of the INFLUENZA A VIRUS.
Molecules on the surface of T-lymphocytes that recognize and combine with antigens. The receptors are non-covalently associated with a complex of several polypeptides collectively called CD3 antigens (ANTIGENS, CD3). Recognition of foreign antigen and the major histocompatibility complex is accomplished by a single heterodimeric antigen-receptor structure, composed of either alpha-beta (RECEPTORS, ANTIGEN, T-CELL, ALPHA-BETA) or gamma-delta (RECEPTORS, ANTIGEN, T-CELL, GAMMA-DELTA) chains.
A family of RNA-BINDING PROTEINS that contain an RNA RECOGNITION MOTIF and two ribonucleoprotein (RNP) domains which bind RNA, in addition to other domains that allow for high affinity binding, sequence specificity, and protein interactions. Examples of RNA recognition motif proteins include HETEROGENEOUS NUCLEAR RIBONUCLEARPROTEINS (hnRNP) and EMBRYONIC LETHAL ABNORMAL-VISION (ELAV) proteins.
Allergies Automimmune Disease Human Papillomavirus (HPV) Immunology Vaccine Immunology is the study of immunity and the defence mechanisms of the body. A greater understanding of immunology is needed to develop vaccines, understand ...
An antibody is a protein produced by the body's immune system when it detects harmful substances, called antigens. Examples of antigens include microorganisms (such as bacteria, fungi, parasites, and viruses) and chemicals. Antibodies may be produc...