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The Journal of Immunology, 2004, 173: 2562-2570.
Copyright © 2004 by The American Association of Immunologists

Human Lymphocytes Interact Directly with CD47 through a Novel Member of the Signal Regulatory Protein (SIRP) Family1

Gary Brooke*, Joanna D. Holbrook{dagger}, Marion H. Brown* and A. Neil Barclay2,*

* Sir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom; and {dagger} GlaxoSmithKline UK Ltd., Uxbridge, United Kingdom

Two closely related proteins, signal regulatory protein {alpha} (SIRP{alpha}; SHPS-1/CD172) and SIRP{beta}, have been described in humans. The existence of a third SIRP protein has been suggested by cDNA sequence only. We show that this third SIRP is a separate gene that is expressed as a protein with unique characteristics from both {alpha} and {beta} genes and suggest that this gene should be termed SIRP{gamma}. We have expressed the extracellular region of SIRP{gamma} as a soluble protein and have shown that, like SIRP{alpha}, it binds CD47, but with a lower affinity (Kd, ~23 µM) compared with SIRP{alpha} (Kd, ~2 µM). mAbs specific to SIRP{gamma} show that it was not expressed on myeloid cells, in contrast to SIRP{alpha} and -{beta}, being expressed instead on the majority of T cells and a proportion of B cells. The short cytoplasmic tail of SIRP{gamma} does not contain any known signaling motifs, nor does it contain a characteristic lysine, as with SIRP{beta}, that is required for DAP12 interaction. DAP12 coexpression is a requirement for SIRP{beta} surface expression, whereas SIRP{gamma} is expressed in its absence. The SIRP{gamma}-CD47 interaction may therefore not be capable of bidirectional signaling as with the SIRP{alpha}-CD47, but, instead, use unidirectional signaling via CD47 only.




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