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Physiological IgM class catalytic antibodies selective for transthyretin amyloid.


ABSTRACT: Peptide bond-hydrolyzing catalytic antibodies (catabodies) could degrade toxic proteins, but acquired immunity principles have not provided evidence for beneficial catabodies. Transthyretin (TTR) forms misfolded ?-sheet aggregates responsible for age-associated amyloidosis. We describe nucleophilic catabodies from healthy humans without amyloidosis that degraded misfolded TTR (misTTR) without reactivity to the physiological tetrameric TTR (phyTTR). IgM class B cell receptors specifically recognized the electrophilic analog of misTTR but not phyTTR. IgM but not IgG class antibodies hydrolyzed the particulate and soluble misTTR species. No misTTR-IgM binding was detected. The IgMs accounted for essentially all of the misTTR hydrolytic activity of unfractionated human serum. The IgMs did not degrade non-amyloidogenic, non-superantigenic proteins. Individual monoclonal IgMs (mIgMs) expressed variable misTTR hydrolytic rates and differing oligoreactivity directed to amyloid ? peptide and microbial superantigen proteins. A subset of the mIgMs was monoreactive for misTTR. Excess misTTR was dissolved by a hydrolytic mIgM. The studies reveal a novel antibody property, the innate ability of IgMs to selectively degrade and dissolve toxic misTTR species as a first line immune function.

SUBMITTER: Planque SA 

PROVIDER: S-EPMC4036335 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature

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Physiological IgM class catalytic antibodies selective for transthyretin amyloid.

Planque Stephanie A SA   Nishiyama Yasuhiro Y   Hara Mariko M   Sonoda Sari S   Murphy Sarah K SK   Watanabe Kenji K   Mitsuda Yukie Y   Brown Eric L EL   Massey Richard J RJ   Primmer Stanley R SR   O'Nuallain Brian B   Paul Sudhir S  

The Journal of biological chemistry 20140319 19


Peptide bond-hydrolyzing catalytic antibodies (catabodies) could degrade toxic proteins, but acquired immunity principles have not provided evidence for beneficial catabodies. Transthyretin (TTR) forms misfolded β-sheet aggregates responsible for age-associated amyloidosis. We describe nucleophilic catabodies from healthy humans without amyloidosis that degraded misfolded TTR (misTTR) without reactivity to the physiological tetrameric TTR (phyTTR). IgM class B cell receptors specifically recogni  ...[more]

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