Inhibition of thrombin-induced platelet aggregation using human single-chain Fv antibodies specific for TREM-like transcript-1

Thromb Haemost. 2007 Jun;97(6):955-63.


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 naïve 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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Antibodies, Monoclonal / genetics
  • Antibodies, Monoclonal / isolation & purification
  • Antibodies, Monoclonal / metabolism
  • Antibodies, Monoclonal / pharmacology*
  • Antibody Specificity
  • Binding, Competitive
  • Blood Platelets / drug effects*
  • Blood Platelets / metabolism
  • Cell Line
  • Dose-Response Relationship, Drug
  • Fibrinolytic Agents / isolation & purification
  • Fibrinolytic Agents / metabolism
  • Fibrinolytic Agents / pharmacology*
  • Humans
  • Immunoglobulin Variable Region / genetics
  • Immunoglobulin Variable Region / isolation & purification
  • Immunoglobulin Variable Region / metabolism
  • Immunoglobulin Variable Region / pharmacology*
  • In Vitro Techniques
  • Peptide Library
  • Platelet Aggregation / drug effects*
  • Receptors, Immunologic / genetics
  • Receptors, Immunologic / immunology
  • Receptors, Immunologic / metabolism*
  • Thrombin / antagonists & inhibitors*
  • Thrombin / metabolism
  • Transfection


  • Antibodies, Monoclonal
  • Fibrinolytic Agents
  • Immunoglobulin Variable Region
  • Peptide Library
  • Receptors, Immunologic
  • TREML1 protein, human
  • Thrombin