Characterization of human platelet binding of recombinant T cell receptor ligand
1 Department of Cell and Developmental Biology, Oregon Health & Science University, Portland, USA
2 Department of Biomedical Engineering, Oregon Health & Science University, Portland, USA
3 Department of Neurology, Oregon Health & Science University, Portland, USA
4 Department of Biochemistry and Molecular Biology, Oregon Health & Science University, Portland, USA
5 Anesthesiology and Perioperative Medicine, Oregon Health & Science University, Portland, USA
6 Neuroimmunology Research, Veterans Affairs Medical Center, Portland, USA
7 Department of Pediatrics, University of Colorado Denver, Aurora, USA
Journal of Neuroinflammation 2010, 7:75 doi:10.1186/1742-2094-7-75Published: 8 November 2010
Recombinant T cell receptor ligands (RTLs) are bio-engineered molecules that may serve as novel therapeutic agents for the treatment of neuroinflammatory conditions such as multiple sclerosis (MS). RTLs contain membrane distal α1 plus β1 domains of class II major histocompatibility complex linked covalently to specific peptides that can be used to regulate T cell responses and inhibit experimental autoimmune encephalomyelitis (EAE). The mechanisms by which RTLs impede local recruitment and retention of inflammatory cells in the CNS, however, are not completely understood.
We have recently shown that RTLs bind strongly to B cells, macrophages, and dendritic cells, but not to T cells, in an antigenic-independent manner, raising the question whether peripheral blood cells express a distinct RTL-receptor. Our study was designed to characterize the molecular mechanisms by which RTLs bind human blood platelets, and the ability of RTL to modulate platelet function.
Our data demonstrate that human blood platelets support binding of RTL. Immobilized RTL initiated platelet intracellular calcium mobilization and lamellipodia formation through a pathway dependent upon Src and PI3 kinases signaling. The presence of RTL in solution reduced platelet aggregation by collagen, while treatment of whole blood with RTL prolonged occlusive thrombus formation on collagen.
Platelets, well-known regulators of hemostasis and thrombosis, have been implicated in playing a major role in inflammation and immunity. This study provides the first evidence that blood platelets express a functional RTL-receptor with a putative role in modulating pathways of neuroinflammation.