Identification of CLEC12B, an inhibitory receptor on myeloid cells.
Activation of immune cells has to be tightly controlled to prevent detrimental hyperactivation. In this regulatory process molecules of the C-type lectin-like family play a central role. Here we describe a new member of this family, CLEC12B. The extracellular domain of CLEC12B shows considerable homology to the activating natural killer cell receptor NKG2D, but unlike NKG2D, CLEC12B contains an immunoreceptor tyrosine-based inhibition motif in its intracellular domain. Despite the homology, CLEC12B does not appear to bind NKG2D ligands and therefore does not represent the inhibitory counterpart of NKG2D. However, CLEC12B has the ability to counteract NKG2D-mediated signaling, and we show that this function is dependent on the immunoreceptor tyrosine-based inhibition motif and the recruitment of the phosphatases SHP-1 and SHP-2. Using monoclonal anti-CLEC12B antibodies we found de novo expression of this receptor on in vitro generated human macrophages and on the human myelo-monocytic cell line U937 upon phorbol 12-myristate 13-acetate treatment, suggesting that this receptor plays a role in myeloid cell function.
Hoffmann
Sabrina C
SC
Institute for Immunology, University of Heidelberg, Im Neuenheimer Feld 305, 69120 Heidelberg, Germany.
Schellack
Carola
C
Textor
Sonja
S
Konold
Stephanie
S
Schmitz
Debora
D
Cerwenka
Adelheid
A
Pflanz
Stefan
S
Watzl
Carsten
C
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D006801:Humans; D037181:Lectins, C-Type / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008954:Models, Biological; D008969:Molecular Sequence Data; D022423:Myeloid Cells / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D011975:Receptors, Mitogen / Q000378:metabolism / Q000502:physiology*; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D020298:U937 Cells
C522578:CLEC12B protein, human; D037181:Lectins, C-Type; D011975:Receptors, Mitogen; D013755:Tetradecanoylphorbol Acetate