Influence of Gm allotype on the IgG subclass response to streptococcal M protein and outer membrane proteins of Moraxella catarrhalis.

The IgG antibody response to streptococcal M protein is distributed between the IgG1 and IgG3 subclasses, however individual sera vary with respect to the relative amounts of these two subclasses. The basis of this variation was investigated. Sera were also analysed for IgG subclass antibodies to the outer membrane proteins (OMP) of Moraxella catarrhalis, as these have also been reported to have a major IgG3 component. The mean percentage of IgG3 was higher in the antibody response to OMP and there was less variability between sera for this antigen than was seen for M protein. Non-specific binding of IgG3 in ELISA, which has been reported for some bacterial proteins (including M protein of some serotypes) was excluded as an explanation for the apparent IgG3 bias of these antibodies. The relative amount of IgG3 antibody to the two antigens showed a positive correlation, suggesting that some individuals tended to make a greater IgG3 response to unrelated antigens. Serial bleeds from two individuals maintained a relatively constant subclass profile over several months, suggesting that time since infection did not play a major role in determining the proportion of IgG1 and IgG3. Gm allotypes for the sera were determined, and found to correlate with both total serum IgG3 concentrations and with IgG subclass composition of specific antibodies. Mean serum IgG3 concentrations were highest in sera typed as Gm(fb/fb) homozygous and lowest in sera typed as Gm(ag/ag) homozygous. Similarly, in the M protein-specific antibodies, the mean percentage of IgG3 was much lower in the Gm(ag/ag) sera than in the Gm(fb/fb) homozygous sera. Sera which typed as Gm(fb/ag) heterozygous were not significantly different from the Gm(fb/fb) homozygous sera for either total serum IgG3 or for M protein-specific IgG3. Moreover, both Gm(fb/fb) homozygous and Gm(fb/ag) heterozygous sera included samples in which IgG1 was the predominant antibody subclass and the percentage of IgG3 was very low. In contrast to the M protein-specific antibodies, for the OMP-specific antibodies there was no correlation between Gm phenotype and the proportion of IgG3. The data suggest that Gm allotype may influence the IgG subclass composition of antibody responses to bacterial surface protein, but that other factors are also likely to be involved.