Our interest in Adhesion-GPCRs started in the mid-90th with the expression cloning of CD97 and the identification of its interacting partner CD55. Since then, we have extensively studied the evolution, expression, structure, interactions, and functions of Adhesion-GPCRs on immune cells. This work has focussed on the EGF-TM7 subfamily members CD97 and EMR1 to 4, and more recently, on the GPR56/GPR97/GPR114 cluster. Using antibody application and gene targeting, we demonstrated roles of CD97 in granulocyte homeostasis and autoimmune pathogenesis. Moreover, we formally proved the interaction of CD97 with CD55 in vivo and showed that CD97 expression levels on circulating blood cells are regulated upon contact with CD55, possibly to restrict CD97-CD55-mediated cell adhesion to tissue sites.
Based on our studies, we suppose that Adhesion-GPCRs function fundamentally different from canonical GPCRs. Key to this hypothesis is the observation that known interacting partners facilitate adhesive contacts but do not necessarily initiate receptor signaling. Our current research focuses on the functioning of Adhesion-GPCRs in relation to (1) immune responses and (2) constitutive versus agonist-dependent signaling.