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


RESULTS
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
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.
Gabrielli
Elena
E
Microbiology Section, Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia, Italy.
Pericolini
Eva
E
Cenci
Elio
E
Ortelli
Federica
F
Magliani
Walter
W
Ciociola
Tecla
T
Bistoni
Francesco
F
Conti
Stefania
S
Vecchiarelli
Anna
A
Polonelli
Luciano
L
D056704:Adaptive Immunity / Q000187:drug effects / Q000276:immunology*; D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology; D002176:Candida albicans / Q000187:drug effects / Q000276:immunology; D002177:Candidiasis / Q000276:immunology / Q000473:pathology; D022801:Complementarity Determining Regions / Q000276:immunology* / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects / Q000276:immunology*; D007143:Immunoglobulin Heavy Chains / Q000276:immunology; D007135:Immunoglobulin Variable Region / Q000276:immunology; D056747:Immunomodulation / Q000187:drug effects; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000201:enzymology / Q000276:immunology; D051379:Mice; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology; D010455:Peptides / Q000276:immunology / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D016019:Survival Analysis; D051197:Toll-Like Receptor 4 / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D015854:Up-Regulation / Q000187:drug effects
D000935:Antifungal Agents; D022801:Complementarity Determining Regions; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D010455:Peptides; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D051057:Proto-Oncogene Proteins c-akt