The four human IgG subclasses are named according to serum prevalence and exhibit relatively high sequence homology (~95%); however, amino acid variation at key positions results in incredible functional diversity. IgG1 and IgG3 subclasses are generally elicited in response to protein antigens associated with viral infections, IgG2 typically targets polysaccharide antigens induced by bacterial infections, and the IgG4 response is associated with repeated exposure to allergens in the absence of an infectious agent. Such diversity among target antigens is reflected in functional differences between subclasses. Whereas IgG1 and IgG3 are potent activators of innate immune effector cells, IgG2 and IgG4 possess more subdued effector activity. The existence of these distinct types of IgGs and their association with divergent immunologic stimuli suggests that human subclass diversity results from evolutionary pressures applied over long time periods. However, the immune system also leverages this diversity over short timescales – displaying rapidly divergent activity profiles of isotypes and subclasses when individuals are repeatedly exposed to foreign antigens, in which multiple rounds of class switch recombination (CSR) can occur. With 29 reported allelic variants defined to date, IgG3 is the most polymorphic of the human IgG subclasses. Unlike other subclasses that vary principally in terms of isolated amino acid substitutions, IgG3 also has structural allotypes that vary in the number of exon repeats (from 1 to 3) in the core hinge. While there is little to suggest direct functional relevance of most allotypic variation among IgG subclasses, associations between IgG allotypes and a wide variety of infections, malignancies, and autoimmune conditions have been observed. Here you can see the cryoEM structure of the hexameric human IgG3 Fc complex (PDB code: 8BTB)

#molecularart ... #immolecular ... #antibosy ... #immunoglobulin ... #igg3 ... #cryoem

Structure rendered with @proteinimaging and depicted with @corelphotopaint