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Molecular Characterization of a Novel Immune Receptor Restricted to the Monocytic Lineage¹

Helena Aguilar^*, Damiana Álvarez-Errico^*, Andrés C. García-Montero, Alberto Orfao, Joan Sayós^2,3,* and Miguel López-Botet^2,3,*

^* Molecular Immunopathology Unit, Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona, Spain; and Servicio de Citometría, Hospital Universitario de Salamanca, Centro de Investigación del Cáncer, and Department of Medicine, Universidad de Salamanca, Salamanca, Spain

Homology basic local alignment search tool search was conducted using a sequence encoding for a novel inhibitory receptor (IREM-1) cloned in our laboratory and a previously described homologous sequence termed CMRF-35. On the basis of this information, we cloned a full length cDNA corresponding to a novel member of this family, termed immune receptor expressed by myeloid cells 2 (IREM-2). The gene, located in chromosome 17q25.1, encodes for a protein of 205 aa that contains an extracellular region comprising an Ig-like domain and a transmembrane region with a positively charged amino acid residue (lysine), that predicted its putative association with an adapter molecule. Indeed, the interaction between IREM-2 and DAP-12 was confirmed in transfected COS-7 cells. By generating specific Abs and using bone marrow and PBMCs, we observed that IREM-2 expression appeared to be restricted to mature hemopoietic cells of the monocytic and myeloid dendritic cell lineages. In vitro differentiation to macrophages or immature dendritic cells down-regulated IREM-2 expression. Upon engagement with the specific mAbs, IREM-2 expressed in rat basophilic leukemia cells together with DAP-12, induced NFAT transcriptional activity; moreover, IREM-2 engagement on monocytes induced TNF- production. Taken together, our results indicate that IREM-2 is a novel activating receptor of the Ig-superfamily in the monocytic lineage.

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