Antibody activity of IgG subclasses

The IgG subclass distribution in specific antibody responses has been found to vary with structure of the antigen (nature of carrier, number and nature of the epitopes, physicochemical properties), its dose and route of entry, as well as with genetic constitution of the host. In contrast to T cell-independent (thymus-independent) antigens,T cell-dependent thymus-dependent) antigens require interaction with helper T lymphocytes in order to stimulate B lymphocytes to antibody production.Interestingly,stimulation of antibody responses towards certain antigens may result in a selective increase in IgG antibodies of certain subclasses (34,35,36). Whereas antibodies against bacterial and viral protein antigens such as tetanus toxoid or outer-membrane components,which are T cell-dependent antigens, can be detected in all four IgG subclasses, IgG1 is the prevailing isotype, sometimes in combination with IgG3(37). Anti-protein antibodies of the IgG2 subclass generally provide only a marginal contribution. On the other hand, IgG antibodies against polysaccharide antigens,which are generally T cell-independent,generally show a much more pronounced subclass distribution: immunization with several encapsulated bacteria leads to an almost exclusive IgG2 anti-polysaccharide response (38). An exception is seen in children under the age of 2-3 years,in whom anti-polysaccharide antibodies have been found to occur in the IgG1 subclass (39).
Repeated, long-term antigenic stimulation with T cell-dependent antigens may lead to a marked IgG4 antibody response(40). In general, anti-viral IgG antibodies are highly restricted to IgG1 and IgG3, with IgG3 antibodies appearing first in the course of infection. The IgG subclass distribution in an anti-bacterial response will be more heterogeneous, since bacteria contain many different antigenic epitopes,with considerable variations in their protein and carbohydrate structures.

The IgG subclass determination of antigen-specific antibodies is still quite cumbersome,although many studies are performed in this area. As a major drawback, no generally accepted international age-related reference values are available. Moreover, different assay systems do not always provide consistent results. The antigen-specific antibodies are mostly determined by means of ELISA, the antigen being coated on a microtiter plate,followed by incubation with the antibodies to be characterized, and finally with enzyme-labelled monoclonal anti-IgG subclass-specific antibody.