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Related Collections Immunobiology Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 May 2001, Vol. 97, No. 9, pp. 2741-2749 IMMUNOBIOLOGY Signal-regulatory protein  (SIRP) but not SIRP is involved in T-cell activation, binds to CD47 with high affinity, and is expressed on immature CD34+CD38 hematopoietic cells Martina Seiffert, Peter Brossart, Charles Cant, Marina Cella, Marco Colonna, Wolfram Brugger, Lothar Kanz, Axel Ullrich, and Hans-Jörg Bühring From the University of Tübingen, Department of Internal Medicine II, Division of Hematology, Immunology, and Oncology, Tübingen, Germany; Max-Planck Institute for Biochemistry, Department of Molecular Biology, Martinsried, Germany; and Basel Institute for Immunology, Basel, Switzerland. Signal-regulatory proteins (SIRPs) represent a new family of inhibitory/activating receptor pairs. They consist of 3 highly homologous immunoglobulin (Ig)-like domains in their extracellular regions, but differ in their cytoplasmic regions by the presence (SIRP) or absence (SIRP) of immunoreceptor tyrosine-based inhibitory motifs (ITIMs). To analyze the differential expression on hematopoietic cells, function and ligand binding capacity of SIRP and SIRP molecules, soluble fusion proteins consisting of the extracellular domains of SIRP1, SIRP2, and SIRP1, as well as SIRP/-specific and SIRP-specific monoclonal antibodies (MoAbs) were generated. In contrast to SIRP1 and SIRP2, no adhesion of SIRP1 to CD47 could be detected by cell attachment assays and flow cytometry. Using deletion constructs of SIRP1, the epitope responsible for SIRP1 binding to CD47 could be confined to the N-terminal Ig-like loop. Flow cytometry analysis with SIRP/- and SIRP-specific MoAbs revealed that SIRP but not SIRP is expressed on CD34+CD38 hematopoietic cells. In addition, a strong SIRP expression was also observed on primary myeloid dendritic cells (DCs) from peripheral blood as well as on in vitro generated DCs. Analysis of the T-cell stimulatory capacity of in vitro generated DCs in the presence of soluble SIRP1 fusion proteins as well as SIRP/-specific and CD47-specific MoAbs revealed a significant reduction of T-cell proliferation in mixed lymphocyte reaction and inhibition of induction of primary T-cell responses under these conditions. In contrast, soluble SIRP or SIRP-specific antibodies had no effect. The data suggest that the interaction of SIRP with CD47 plays an important role during T-cell activation and induction of antigen-specific cytotoxic T-lymphocyte responses by DCs. © 2001 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: F. Guimont-Desrochers, C. Beauchamp, G. Chabot-Roy, V. Dugas, E. E. 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