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Nature and Nurture of Catalytic Antibodies

  • Sudhir PaulEmail author
  • Stephanie A. Planque
  • Yasuhiro Nishiyama
  • Carl V. Hanson
  • Richard J. Massey
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 750)

Abstract

Immunoglobulins (antibodies) frequently express constitutive functions. Two such functions are nucleophilic catalysis and the reversible binding to B-cell superantigens. Constitutive or “naturally-occurring” antibodies are produced spontaneously from germline genetic information. The antibody structural elements mediating the constitutive functions have originated over millions of years of phylogenic evolution, contrasting with antigen-driven, somatic sequence diversification of the complementarity determining regions (CDR) that underlies the better-known high affinity antigen binding function of antibodies. Often, the framework regions (FRs) play a dominant role in antibody constitutive functions. Catalytic antibody subsets with promiscuous, autoantigen-directed and microbe-directed specificities have been identified. Mucosal antibodies may be specialized to express high-level catalytic activity against microbes transmitted by the mucosal route, exemplified by constitutive production of IgA class antibodies in mucosal secretions that catalyze the cleavage of HIV gp120. Catalytic specificity can be gained by constitutive noncovalent superantigen binding at the FRs and by adaptive development of noncovalent classical antigen or superantigen binding, respectively, at the CDRs and FRs. Growing evidence suggests important functional roles for catalytic antibodies in homeostasis, autoimmune disease and protection against infection. Adaptive antibody responses to microbial superantigens are proscribed underphysiological circumstances. Covalent electrophilic immunogen binding to constitutively expressed nucleophilic sites in B-cell receptors bypasses the restriction on adaptive antibody production, and simultaneous occupancy of the CDR binding site by a stimulatory antigenic epitope can also overcome the downregulatory effect of superantigen binding at the FRs. These concepts may be useful for developing novel vaccines that capitalize and improve on constitutive antibody functions for protection against microbes.

Keywords

Vasoactive Intestinal Peptide Antigen Binding Complementarity Determine Region Catalytic Antibody Clonal Selection Theory 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Landes Bioscience and Springer Science+Business Media 2012

Authors and Affiliations

  • Sudhir Paul
    • 1
    • 2
    Email author
  • Stephanie A. Planque
    • 1
  • Yasuhiro Nishiyama
    • 1
  • Carl V. Hanson
    • 3
  • Richard J. Massey
    • 2
  1. 1.Chemical Immunology Research Center, Department of PathologyUniversity of Texas—Houston Medical SchoolHoustonUSA
  2. 2.Covalent Bioscience IncHoustonUSA
  3. 3.Viral and Rickettsial Disease LaboratoryCalifornia Department of Public HealthRichmondUSA

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