Inhibition of thrombin-induced platelet aggregation using human single-chain Fv antibodies specific for TREM-like transcript-1
Giomarelli, B.; Washington, V.A.; Chisholm, M.M.; Quigley, L.; McMahon, J.B.; Mori, T.; McVicar, D.W.
Thrombosis and Haemostasis 97(6): 955-963
2007
ISSN/ISBN: 0340-6245 PMID: 17549298 Document Number: 606395
TREM-like transcript-1 (TLT-1) is a novel platelet membrane receptor, which has been recently characterized in mice.TLT-1 is expressed exclusively in platelets and megakaryocytes, and its expression is dramatically upregulated upon platelet activation, suggesting that it plays a unique role in hemostasis and/or thrombosis. In this study we identified and characterized highly specific human monoclonal antibodies that bind to TLT-1 by screening a naive library of single chain Fv fragments (scFvs) displayed on filamentous phage (Thomlinson I library).These scFvs detected plate-bound TLT-1, captured soluble TLT-1, and readily reacted with cell-bound TLT-1 on transfectants and primary human platelets. Most importantly, anti-TLT-1 scFvs inhibited thrombin-mediated human platelet aggregation. This inhibition was specific for thrombin-induced aggregation and was reversible with higher doses of agonist.These data are the first to demonstrate a biological role for TLT-1 and its potential as a therapeutic target.The human scFvs isolated in this study may represent novel anti-platelet therapeutic agents.