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.

Antibody complementarity-determining regions (CDRs): a bridge between adaptive and innate immunity / Gabrielli, E.; Pericolini, Eva; Cenci, E.; Ortelli, F.; Magliani, W.; Ciociola, T.; Bistoni, F.; Conti, S.; Vecchiarelli, A.; Polonelli, L.. - In: PLOS ONE. - ISSN 1932-6203. - 4:12(2009), pp. 1-12. [10.1371/journal.pone.0008187]

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

PERICOLINI, Eva;
2009

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.
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Antibody complementarity-determining regions (CDRs): a bridge between adaptive and innate immunity / Gabrielli, E.; Pericolini, Eva; Cenci, E.; Ortelli, F.; Magliani, W.; Ciociola, T.; Bistoni, F.; Conti, S.; Vecchiarelli, A.; Polonelli, L.. - In: PLOS ONE. - ISSN 1932-6203. - 4:12(2009), pp. 1-12. [10.1371/journal.pone.0008187]
Gabrielli, E.; Pericolini, Eva; Cenci, E.; Ortelli, F.; Magliani, W.; Ciociola, T.; Bistoni, F.; Conti, S.; Vecchiarelli, A.; Polonelli, L.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11380/1120026
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