Human Immunoglobulin G and Immunoglobulin G Subclasses: Biochemical, Genetic, and Clinical Aspects

Abstract

Human IgG consists of two identical heavy (H) chains and two identical light (L) chains joined by interchain disulfide bridges. Heterogeneity in the amino acid sequences of the H and L polypeptides results in at least three types of IgG variants at the structural and genetic levels. The four isotypic forms are IgG1, IgG2, IgG3, and IgG4, which share extensive homologies in the primary structure of their H chains. As a result, the subclasses cross-react antigenically, but they can be differentiated on the basis of subtle architectural dissimilarities. The biological and effector properties of the IgG isotypes have been associated, in part, with their structural differences. Genes determining the synthesis of human IgG heavy chains are located on chromosome 14. In several clinical situations the isotypes appear to be regulated or expressed in patterns reflecting the gene arrangement. The numeric designations of the subclasses correspond to the order of their proportional amounts in healthy adult serum: IgG1 greater than IgG2 greater than IgG3 greater than IgG4. Awareness of the importance of the roles of the four IgG isotypes in human health has steadily increased since they were first described in the 1960s. The recognition that deficits or increases in selected IgG subclasses may have clinical consequences has prompted considerable interest in quantifying the four isotypes in clinical specimens. In particular, deficiencies of IgG2, IgG3, and IgG4, singly or combined, are associated with chronic infections which may not be readily recognized in otherwise healthy people with normal serum total IgG concentrations. Different assay methods using polyclonal or monoclonal antisera with various calibrants have been applied; however, no standardized method exists at the present. IgG deficits are associated with gene defects and are acquired in secondary immunodeficiencies in conjunction with other disorders. IgG isotype selectivity has been recognized in autoimmune diseases and in response to carbohydrate and protein antigens derived from pathogenic microorganisms and common allergens.

Vaccination with NY-ESO-1 protein and CpG in Montanide induces integrated antibody/Th1 responses and CD8 T cells through cross-priming

“…Consistent with this concept, vaccine-induced IgG predominantly were IgG1 and IgG3, the most prominent IgG type 1 human subclasses, involved in functions such as complement activation, mediation of antibody-dependent cellular cytotoxicity (ADCC), and opsonization (22).…”

Immunology of Diseases Associated withMalasseziaSpecies

“…Despite using a more sensitive technique than those used in previous studies, the authors did not document any significant differences in the titers of any of the classes of immunoglobulins between patients and controls. Levels of the four IgG subclasses were similar, contrasting with the normal proportions of IgG1 through IgG4 in serum, which were 65, 25, 6, and 4%, respectively (326). IgG4 may be a marker of chronic antigen exposure, occurring as a late antibody response to high levels of antigen (389), and so both patients and normals are chronically exposed to the antigens of Malassezia.…”

Vaccination with Ep-CAM Protein or Anti-Idiotypic Antibody Induces Th1-Biased Response against MHC Class I- and II-Restricted Ep-CAM Epitopes in Colorectal Carcinoma Patients

“…The subclass responses were predominantly IgG1 and IgG3. In humans, a Th1-polarized immune response is associated with IgG1 and IgG3 (18), which are the most effective subclasses mediating phagocytosis, complement-dependent cytolysis, and Ab-dependent cellular cytotoxicity (30). After booster vaccination, IgG4 also emerged, most likely reflecting prolonged antigenic stimulation (31).…”