Ficolin-1 is a soluble pattern recognition molecule synthesized by myeloid cells and capable of activating the lectin pathway of complement on the surface of pathogens. It is tethered to the membranes of monocytes and granulocytes; however, the biological significance of cell-associated ficolin-1 is unknown. Recognition of healthy host cells by a pattern recognition molecule constitutes a potential hazard to self cells and tissues, emphasizing the importance of further elucidating the reported self-recognition. In the current study we investigated the potential recognition of lymphocytes by ficolin-1 and demonstrated that CD56(dim) NK-cells and both CD4(+) and CD8(+) subsets of activated T-cells were recognized by ficolin-1. In contrast we did not detect binding of ficolin-1 to CD56(bright) NK-cells, NKT-cells, resting T-cells or B-cells. Furthermore, we showed that the protein-lymphocyte interaction occurred via the pathogen-recognition domain of ficolin-1 to sialic acid on the cell surface. Thus, the differential binding of ficolin-1 to lymphocyte subsets suggests ficolin-1 as a novel link between innate and adaptive immunity. Our results provide new insight about the recognition properties of ficolin-1 and point toward additional immune modulating functions of the molecule besides its role in pathogen recognition.