No abstract

An allosteric mechanism for the generation of long-distance structural alterations in Fab fragments of antibodies in immune complexes has been postulated and tested in theoretical and experimental analysis. The flexing and/or torsionderived forces exerted on the elbow region in Fab arms of bivalent antibodies upon binding to antigen were assumed to drive the disruption of hydrogen bonds which stabilize N-and C-terminal chain fragments in V-domains. This allows an extra movement in the elbow followed by a relaxation in the Fab arm and may generate longdistance effects if, in particular, the structural changes are generated asymmetrically involving one chain of the Fab arm only. This mechanism was studied by simulation of molecular dynamics. The local instability in the area involving the site of packing of the N-terminal chain fragment allows penetration and binding of the supramolecular dye Congo red that hence becomes an indicator of the initiated relaxation process and is also the prospective ligand in studies of designing drugs. The susceptibility to dye binding was observed in complexation of bivalent antibodies only, supplying the evidence that constraints associating the interaction with randomly distributed antigenic determinants drive the local structural changes in the V-domain followed by longdistance effects.

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Increasing infections with Monkeypox and Cowpox viruses pose a continuous and growing threat to human health. The standard method for detecting poxvirus neutralizing antibodies is the plaque-reduction neutralization test that is specific but also time-consuming and laborious. Therefore, a rapid and reliable method was developed to determine neutralizing antibody titers within twelve hours. The new assay measures viral mRNA transcription as a marker for actively replicating virus after incomplete neutralization using real-time PCR.

The results of this study confirm the heavy chain-related propensity of some monoclonal immunoglobulins to aggregate and precipitate. The simplicity of the technique may improve clinical diagnosis and facilitate predictions of disease complications.