Antibody complementarity-determining regions (CDRs): a bridge between adaptive and innate immunity

PLoS One. 2009 Dec 4;4(12):e8187. doi: 10.1371/journal.pone.0008187.

Abstract

Background: It has been documented that, independently from the specificity of the native antibody (Ab) for a given antigen (Ag), complementarity determining regions (CDR)-related peptides may display differential antimicrobial, antiviral and antitumor activities.

Methodology/principal findings: In this study we demonstrate that a synthetic peptide with sequence identical to V(H)CDR3 of a mouse monoclonal Ab (mAb) specific for difucosyl human blood group A is easily taken up by macrophages with subsequent stimulation of: i) proinflammatory cytokine production; ii) PI3K-Akt pathway and iii) TLR-4 expression. Significantly, V(H)CDR3 exerts therapeutic effect against systemic candidiasis without possessing direct candidacidal properties.

Conclusions/significance: These results open a new scenario about the possibility that, beyond the half life of immunoglobulins, Ab fragments may effectively influence the antiinfective cellular immune response in a way reminiscent of regulatory peptides of innate immunity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptive Immunity / drug effects
  • Adaptive Immunity / immunology*
  • Animals
  • Antifungal Agents / pharmacology
  • Candida albicans / drug effects
  • Candida albicans / immunology
  • Candidiasis / immunology
  • Candidiasis / pathology
  • Complementarity Determining Regions / immunology*
  • Complementarity Determining Regions / pharmacology
  • Enzyme Activation / drug effects
  • Humans
  • Immunity, Innate / drug effects
  • Immunity, Innate / immunology*
  • Immunoglobulin Heavy Chains / immunology
  • Immunoglobulin Variable Region / immunology
  • Immunomodulation / drug effects
  • Macrophages, Peritoneal / drug effects
  • Macrophages, Peritoneal / enzymology
  • Macrophages, Peritoneal / immunology
  • Mice
  • Neutrophils / drug effects
  • Neutrophils / immunology
  • Peptides / immunology
  • Peptides / pharmacology
  • Proto-Oncogene Proteins c-akt / metabolism
  • Survival Analysis
  • Toll-Like Receptor 4 / genetics
  • Tumor Necrosis Factor-alpha / biosynthesis
  • Up-Regulation / drug effects

Substances

  • Antifungal Agents
  • Complementarity Determining Regions
  • Immunoglobulin Heavy Chains
  • Immunoglobulin Variable Region
  • Peptides
  • Toll-Like Receptor 4
  • Tumor Necrosis Factor-alpha
  • Proto-Oncogene Proteins c-akt