Original Article

Springer Seminars in Immunopathology

, Volume 26, Issue 4, pp 485-503

First online:

Antibodies as defensive enzymes

  • Sudhir PaulAffiliated withChemical Immunology and Therapeutics Research Center, Department of Pathology and Laboratory Medicine, University of Texas-Houston Medical School Email author 
  • , Yasuhiro NishiyamaAffiliated withChemical Immunology and Therapeutics Research Center, Department of Pathology and Laboratory Medicine, University of Texas-Houston Medical School
  • , Stephanie PlanqueAffiliated withChemical Immunology and Therapeutics Research Center, Department of Pathology and Laboratory Medicine, University of Texas-Houston Medical School
  • , Sangeeta KarleAffiliated withChemical Immunology and Therapeutics Research Center, Department of Pathology and Laboratory Medicine, University of Texas-Houston Medical School
  • , Hiroaki TaguchiAffiliated withChemical Immunology and Therapeutics Research Center, Department of Pathology and Laboratory Medicine, University of Texas-Houston Medical School
  • , Carl HansonAffiliated withRickettsial Disease Lab, California Department of Health Services
  • , Marc E. WekslerAffiliated withDepartment of Medicine, Weill Medical College of Cornell University

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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