A novel a / b T-cell subpopulation defined by recognition of EPCR 1 2

20 T-cell self-recognition of antigen presenting molecules is led by antigen-dependent or 21 independent mechanisms. The endothelial protein C receptor (EPCR) shares remarkable 22 similarity with CD1d, including a lipid binding cavity. We have identified EPCR-specific a/b 23 T-cells in the peripheral blood of healthy donors. The average frequency in the CD3+ 24 leukocyte pool is comparable to other autoreactive T-cell subsets that specifically bind MHC25 like receptors. Alteration of the EPCR lipid cargo, revealed by X-ray diffraction studies, 26 points to a prevalent, yet not exclusive, lipid-independent self-recognition. In addition, we 27 solve the EPCR lipidome, and detect species not yet described as EPCR ligands. These 28 studies report, for the first time, novel recognition by circulating a/b T-cells and provide 29 grounds for EPCR and lipid mediated T-cell restriction. 30