Springer Seminars in Immunopathology

, Volume 26, Issue 4, pp 485–503 | Cite as

Antibodies as defensive enzymes

  • Sudhir Paul
  • Yasuhiro Nishiyama
  • Stephanie Planque
  • Sangeeta Karle
  • Hiroaki Taguchi
  • Carl Hanson
  • Marc E. Weksler
Original Article

Abstract

Antibodies (Abs) and enzymes are structural and functional relatives. Abs with promiscuous peptidase activity are ubiquitous in healthy humans, evidently derived from germline variable domain immunoglobulin genes encoding the serine protease-like nucleophilic function. Exogenous and endogenous electrophilic antigens can bind the nucleophilic sites covalently, and recent evidence suggests that immunization with such antigens can induce proteolytic antibodies. Previously, Ab catalytic activities have been linked to pathogenic autoimmune reactions, but recent studies indicate that proteolytic Abs may also serve beneficial functions. An example is the rapid and selective cleavage of the HIV-1 coat protein gp120 by IgMs found in uninfected humans. The selectivity of this reaction appears to derive from recognition of gp120 as a superantigen. A second example is the cleavage of amyloid β-peptide by IgM and IgG from aged humans, a phenomenon that may represent a specific proteolytic response to a neurotoxic endogenous peptide implicated in the pathogenesis of Alzheimer’s disease.

Keywords

Abzymes Catalytic antibodies Serine proteases Autoimmune disease HIV infection 

Notes

Acknowledgements

Supported by NIH grants AI31268 and AI058865, and grants from Dana Foundation and Alzheimer’s Association. We thank Laura Nixon for administering our research.

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Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  • Sudhir Paul
    • 1
  • Yasuhiro Nishiyama
    • 1
  • Stephanie Planque
    • 1
  • Sangeeta Karle
    • 1
  • Hiroaki Taguchi
    • 1
  • Carl Hanson
    • 2
  • Marc E. Weksler
    • 3
  1. 1.Chemical Immunology and Therapeutics Research Center, Department of Pathology and Laboratory MedicineUniversity of Texas-Houston Medical SchoolHoustonUSA
  2. 2.Rickettsial Disease LabCalifornia Department of Health ServicesRichmondUSA
  3. 3.Department of MedicineWeill Medical College of Cornell UniversityNew YorkUSA

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