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 VHCDR3 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, VHCDR3 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.

Antibody Complementarity-Determining Regions (CDRs): A Bridge between Adaptive and Innate Immunity / E., Gabrielli; E., Pericolini; E., Cenci; F., Ortelli; Magliani, Valter; Ciociola, Tecla; F., Bistoni; Conti, Stefania; A., Vecchiarelli; Polonelli, Luciano. - In: PLOS ONE. - ISSN 1932-6203. - 4:(2009), pp. e8187-1-e8187-12. [10.1371/journal.pone.0008187]

Antibody Complementarity-Determining Regions (CDRs): A Bridge between Adaptive and Innate Immunity

MAGLIANI, Valter;CIOCIOLA, Tecla;CONTI, Stefania;POLONELLI, Luciano
2009-01-01

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 VHCDR3 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, VHCDR3 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.
Antibody Complementarity-Determining Regions (CDRs): A Bridge between Adaptive and Innate Immunity / E., Gabrielli; E., Pericolini; E., Cenci; F., Ortelli; Magliani, Valter; Ciociola, Tecla; F., Bistoni; Conti, Stefania; A., Vecchiarelli; Polonelli, Luciano. - In: PLOS ONE. - ISSN 1932-6203. - 4:(2009), pp. e8187-1-e8187-12. [10.1371/journal.pone.0008187]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11381/2304329
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