A high affinity human antibody antagonist of P-selectin mediated rolling.
We have characterized the IgG form of a previously isolated and engineered single-chain Fv (scFv), named RR2r3s4-1, that binds to human PSGL-1. This fully human IgG was determined to have a Kd of 1.8+/-0.7 nM by fluorescence quenching titration. It better inhibits P-selectin-PSGL-1 interactions than a commercially available murine monoclonal antibody KPL1 and better inhibits neutrophil rolling than KPL1. Thus, RR2r3s4-1 is the most effective antibody at inhibiting P-selectin-PSGL-1 interactions known. Specificity analysis reveals that RR2r3s4-1 does not cross react with murine PSGL-1 and thus requires more than tyrosine sulfate for binding to human PSGL-1. This evidence demonstrates the therapeutic potential of this antibody as a potent anti-inflammatory therapeutic.
Swers
Jeffrey S
JS
Department of Chemical Engineering, Massachusetts Institute of Technology 66-552, 25 Ames Street, Cambridge, MA 02139, USA.
Widom
Angela
A
Phan
Uyen
U
Springer
Timothy A
TA
Wittrup
K Dane
KD
D000818:Animals; D019556:COS Cells; D002465:Cell Movement / Q000276:immunology*; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D006801:Humans; D007074:Immunoglobulin G / Q000737:chemistry* / Q000276:immunology*; D018375:Neutrophil Activation / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology*; D019007:P-Selectin / Q000737:chemistry* / Q000276:immunology*
D007074:Immunoglobulin G; D019007:P-Selectin