![]() For those antigens, class switching tends to be IgG1 or IgG3, but can also be IgG4 or IgE. For example, protein antigens usually trigger B-cells receiving T-cell help through MHC-class II expressed by the B-cell. Besides direct B-cell triggering by the antigen itself, a number of secondary signals will influence differentiation of the B-cell, including recognition by pattern-recognition receptors like Toll-like receptors and cytokines produced by other lymphocytes and antigen-presenting cells ( 5, 6). The route by which an antigen enters our body and its chemical composition steers the (secondary) immune reaction into preferential patterns of class switching. All in all, the acquired variability within the Ig locus seems to have selected for beneficial changes during evolution for optimizing or fine tuning the antibody-mediated immune response. More often, one or more of the IgG subclass levels – predominantly IgG2 and/or IgG4 – are below the normal range in healthy individuals ( 4), which sometimes leads to an impaired response to infections with encapsulated bacteria as will be discussed below. This can be caused by complete isotype- or subclass deficiency due to deletions in the Ig loci of chromosome 14, but this is rare ( 3). Selective subclass deficiencies are usually not detrimental to the individual, but do sometimes lead to enhanced susceptibility toward specific classes of pathogens. In addition, IgG antibody responses to different types of antigens leads to marked skewing toward one of the subclasses. ![]() Although they are more than 90% identical on the amino acid level, each subclass has a unique profile with respect to antigen binding, immune complex formation, complement activation, triggering of effector cells, half-life, and placental transport. Differences in structure and function of IgG subclasses are summarized in Table 1. The subclasses of IgG were discovered in the 1960s following extensive studies using specific rabbit antisera against human IgG myeloma proteins ( 1). IgG can be further divided in four subclasses, named, in order of decreasing abundance IgG1, IgG2, IgG3, and IgG4 ( 1). These closely related glycoproteins, composed of 82–96% protein and 4–18% carbohydrate, differ in heavy chain structure and have different effector functions. It is the major class of the five classes of immunoglobulins in human beings, IgM, IgD, IgG, IgA, and IgE. Immunoglobulin G (IgG) is one of the most abundant proteins in human serum, accounting for about 10–20% of plasma protein. How these properties, IgG-polymorphisms and post-translational modification of the antibodies in the form of glycosylation, affect IgG-function will be the focus of the current review. However, FcRn is also expressed in myeloid cells, where it participates in both phagocytosis and antigen presentation together with classical FcγR and complement. The Fc-regions also contain a binding epitope for the neonatal Fc receptor (FcRn), responsible for the extended half-life, placental transport, and bidirectional transport of IgG to mucosal surfaces. As a result, the different subclasses have different effector functions, both in terms of triggering FcγR-expressing cells, resulting in phagocytosis or antibody-dependent cell-mediated cytotoxicity, and activating complement. These regions are involved in binding to both IgG-Fc receptors (FcγR) and C1q. ![]() The four subclasses, IgG1, IgG2, IgG3, and IgG4, which are highly conserved, differ in their constant region, particularly in their hinges and upper CH2 domains. Of the five immunoglobulin isotypes, immunoglobulin G (IgG) is most abundant in human serum.
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