Mycoplasma immunoglobulin binding protein universally binds human antibodies, thereby reducing Fab arm flexibility and displacing antigens in immune complexes

Kadava, T.; Bar Barroeta, A.; de Haas, C. J. C.; Rooijakkers, S.; Strasser, J.; Preiner, J.; Nordgren, M.; Lood, R.; Heck, A. J. R.

doi:10.64898/2026.06.12.731821

bioRxiv · 10.64898/2026.06.12.731821

Mycoplasma immunoglobulin binding protein universally binds human antibodies, thereby reducing Fab arm flexibility and displacing antigens in immune complexes

Kadava, T.·Bar Barroeta, A.·de Haas, C. J. C.·Rooijakkers, S.·Strasser, J.·Preiner, J.·Nordgren, M.·Lood, R.·Heck, A. J. R.

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Abstract

Mycoplasma immunoglobulin binding (MIB) protein plays a key role in immune evasion across several Mycoplasma species. MIB tightly interacts with the Fab domain of immunoglobulin G, inducing conformational changes that disrupt the antigen-binding site. Here, we reveal that MIB binds strongly and universally to all major isotypes and subclasses of human antibodies and can thus serve as a bait protein to efficiently deplete antibodies from serum. Our results demonstrate strong interactions between MIB and a diverse set of both recombinant monoclonal and endogenous polyclonal antibodies, the latter purified from serum or colostrum. All antibodies, including IgG and IgA monomers, J-chain coupled IgA dimers, and IgM pentamers, consistently bind two copies of MIB per antibody protomer. Using cross-linking mass spectrometry, we pinpoint that antibody-MIB interactions involve conserved regions of the variable and constant antibody domains, independent of isotype. Furthermore, we demonstrate that MIB not only disrupts the Fab-antigen interaction but also restricts Fab flexibility, as visualized by atomic force microscopy. Conversely, MIB does not affect Fc-mediated protein interactions, as exemplified by the successful reconstitution of a 36-subunit immune complex, (IgG)6-(MIB)12-C1q.

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Kadava, T., Bar Barroeta, A., de Haas, C. J. C., Rooijakkers, S., Strasser, J., Preiner, J., Nordgren, M., Lood, R., Heck, A. J. R.. 2026-06-15. Mycoplasma immunoglobulin binding protein universally binds human antibodies, thereby reducing Fab arm flexibility and displacing antigens in immune complexes. https://doi.org/10.64898/2026.06.12.731821

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