RT Journal Article SR Electronic T1 A novel α/β T-cell subpopulation defined by recognition of EPCR JF bioRxiv FD Cold Spring Harbor Laboratory SP 2021.07.01.450412 DO 10.1101/2021.07.01.450412 A1 Elena Erausquin A1 María Morán-Garrido A1 Jorge Saiz A1 Coral Barbas A1 Gilda Dichiara-Rodríguez A1 Natalia Ramírez A1 Jacinto López-Sagaseta YR 2021 UL http://biorxiv.org/content/early/2021/07/01/2021.07.01.450412.abstract AB T-cell self-recognition of antigen presenting molecules is led by antigen-dependent or independent mechanisms. The endothelial protein C receptor (EPCR) shares remarkable similarity with CD1d, including a lipid binding cavity. We have identified EPCR-specific α/β T-cells in the peripheral blood of healthy donors. The average frequency in the CD3+ leukocyte pool is comparable to other autoreactive T-cell subsets that specifically bind MHC-like receptors. Alteration of the EPCR lipid cargo, revealed by X-ray diffraction studies, points to a prevalent, yet not exclusive, lipid-independent self-recognition. In addition, we solve the EPCR lipidome, and detect species not yet described as EPCR ligands. These studies report, for the first time, novel recognition by circulating α/β T-cells and provide grounds for EPCR and lipid mediated T-cell restriction.Competing Interest StatementThe authors have declared no competing interest.