Native Human IgG1 protein

Specifications

Form

Liquid

General info

Function

Constant region of immunoglobulin (Ig) heavy chains. Igs are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral immunity, the membrane-bound Igs serve as receptors, which upon binding to a specific antigen trigger the clonal expansion and differentiation of B lymphocytes into Ig-secreting plasma cells. Secreted Igs known as antibodies mediate the effector phase of humoral immunity by blocking the interaction of infectious antigens with cellular receptors (via the antigen-binding region) and eliciting effector mechanisms that lead to pathogen neutralization (via the constant region) (PubMed : 17576170, PubMed : 20176268, PubMed : 22158414). The antigen-binding region is formed by the variable domain of one heavy chain paired with the variable domain of its associated light chain. Each Ig molecule has two antigen-binding sites with remarkable affinity for a particular antigen due to V-(D)-J rearrangement, somatic hypermutations and affinity maturation of the variable domains upon antigen exposure (PubMed : 17576170, PubMed : 20176268, PubMed : 22158414). The constant region defines the Ig isotype that perform distinct sets of effector functions. B cells diversify and rearrange their Ig constant regions through class-switch recombination, a process by which the constant region is switched from one Ig isotype to another, namely from IgM and IgD to IgG, IgA and IgE (PubMed : 17576170, PubMed : 20176268, PubMed : 22158414). The constant region of Ig gamma-1 (IgG1) isotype interacts (via the fragment crystallizable, Fc) with receptors on innate immune cells and the complement system to mediate humoral effector functions, including antibody-dependent cellular cytotoxicity or phagocytosis, complement-dependent cytotoxicity and inflammatory responses.

Post-translational modifications

N-glycosylated. Carries predominantly biantennary complex-type glycans attached at Asn-180 residue on the Fc region of each heavy chain. Unique Fc glycan profiles found in secreted IgGs are induced in an antigen-specific way, likely programmed during B cell priming to mount an appropriate Ig effector response (PubMed:10818239, PubMed:10917521, PubMed:21768335, PubMed:22184099, PubMed:25561553, PubMed:29133956, PubMed:29445378). The core glycan is composed of two sequential N-acetylglucosamine (GlcNAc) moieties followed by a central mannose (Man) from which two additional Man residues branch out (alpha1,3 and alpha1,6 antennae) each capped with a GlcNAc. Additional sugar molecules can be added to generate over 30 possible glycans. Such sugar modifications include the addition of one fucose at the initial GlcNAc, galactose (Gal) and sialic acid (Neu5Ac) residues at antennary GlcNAc or a bisecting GlcNAc to the core Man (PubMed:10818239, PubMed:22184099, PubMed:29133956, PubMed:38383719). Variable addition of sugars account for different IgG functional states associated with antibody-dependent cellular cytotoxicity or phagocytosis and inflammatory responses such as complement activation and cytokine secretion. Fc N-glycan diversity is further enhanced by asymmetric glycan pairing on the heavy chains (PubMed:10818239, PubMed:20357243, PubMed:22184099, PubMed:29133956). Fc N-glycan sialylation is linked to anti-inflammatory effects. It regulates Fc effector functions through conformational changes leading to preferential interaction with type II Fc receptors while reducing binding to type I Fc receptors. During plasmablast response, sialylated Fc domains within immune complexes signal via FCER2/CD23 and drive the selection of B cells with high affinity for antigen (PubMed:18420934, PubMed:22184099, PubMed:25733881, PubMed:26140596). Fc Igs carrying afucosylated N-glycans preferentially activate FCGR3A, antigen-dependent cellular cytotoxicity and antitumor immunity (PubMed:12427744, PubMed:21768335, PubMed:28566370, PubMed:30061887, PubMed:36867679).. (Microbial infection) Deglycosylation on Asn-180 by S. pyogenes EndoS or Endos2 endoglucosidases prevents interaction between immunoglobulin-gamma (IgG) and Fc receptors, impairing ability to activate the complement pathway.