Antibodies as defensive enzymes.
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 beta-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.
Paul
Sudhir
S
Chemical Immunology and Therapeutics Research Center, Department of Pathology and Laboratory Medicine, University of Texas-Houston Medical School, MSB 2.250, 6431 Fannin, Houston, TX 77030, USA. Sudhir.Paul@uth.tmc.edu
Nishiyama
Yasuhiro
Y
Planque
Stephanie
S
Karle
Sangeeta
S
Taguchi
Hiroaki
H
Hanson
Carl
C
Weksler
Marc E
ME
D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D000818:Animals; D017151:Antibodies, Catalytic / Q000737:chemistry / Q000378:metabolism*; D001666:Binding Sites, Antibody; D004798:Enzymes / Q000276:immunology / Q000378:metabolism; D015699:HIV Envelope Protein gp120 / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate; D066298:In Vitro Techniques; D051379:Mice; D018448:Models, Immunological; D008958:Models, Molecular; D008969:Molecular Sequence Data
D016229:Amyloid beta-Peptides; D017151:Antibodies, Catalytic; D004798:Enzymes; D015699:HIV Envelope Protein gp120