Structural differences between Variant FS and wild type are also reflected in the loss of binding of the variant to FccRII and FccRIII receptors. Altogether, the results indicate that in Variant FS the carbohydrates and protein form fewer contacts, and that disruption of carbohydrate-pi Cantharidin interactions leads to structural changes and to a significant reduction in antibody stability. In contrast to Variant FS, Variant FY carries a conservative mutation with respect to CH-pi interactions, and remains fairly stable. Variant FY trails wild type by only 1�C2% in accelerated aggregation experiments at 12 and 24 hrs, and narrowly surpasses wild type at 36 hrs. We do not believe that the observed differences in aggregation kinetics are a result of the higher G2 glycosylation levels of Variant FY because another wild type sample has similar G2 glycosylation levels. The change of aggregation kinetics in Variant FY in comparison to wild type may occur if the introduced mutation stabilizes a subpopulation of the original sample or an intermediate. Antibody molecules can assume a number of orientations during aggregation. Our results point to interactions in the CH2 domain as a mechanism of antibody aggregation. Such interactions may occur by parallel, angled or anti-parallel stacking of molecules. We suggest the angled orientation as an alternative to the parallel stacking for improved 3-dimensional distribution of the Fab domains. A salient feature in all three examples is the presence of intermolecular interactions between protein Cephalomannine patches that become exposed due to protein-carbohydrate fluctuations. For simplicity, here we discuss models of interactions between the dynamically exposed patches, although in reality such patches may interact also with existing surface-exposed patches. In the parallel and angled orientations, the molecules are only partially overlapping, so that the front patch of one molecule can interact with the back patch of the other molecule; in contrast, the anti-parallel orientation has both Chain A and Chain B of the molecules overlap to facilitate proximity of the patches from one of the chains.