Expression and function of CD300 in NK cells.
The killing activity of NK cells is regulated by signals derived from inhibitory and activating NK cell receptors, including the CD300 family of proteins. CD300a was reported to be expressed on all NK cells and to deliver an inhibitory signal upon binding to a yet unknown ligand/s. The CD300a protein contains four ITIMs and is highly homologous to CD300c. Little is known about the function and distribution of these two receptors and the identity of their ligand/s. In this article, we show that CD300a is indeed an inhibitory receptor expressed by human NK cells, but surprisingly, we show that not all NK clones are inhibited in a CD300a-dependent manner. We demonstrate, using a panel of 13 new anti-CD300a and CD300c Abs that we generated, that CD300a and CD300c are indistinguishable on the surface of NK cells. Using mutational-analysis survey, we show that tyrosine 267 located in the third ITIM motif of the CD300a protein is important for the inhibitory function of CD300a.
Lankry
Dikla
D
Lautenberg Center for General and Tumor Immunology, BioMedical Research Institute, Hadassah Medical School, Hebrew University, Jerusalem, Israel.
Simic
Hrvoje
H
Klieger
Yair
Y
Levi-Schaffer
Francesca
F
Jonjic
Stipan
S
Mandelboim
Ofer
O
D000409:Alanine / Q000378:metabolism; D020816:Amino Acid Motifs / Q000276:immunology; D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D015703:Antigens, CD / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology*; D001666:Binding Sites, Antibody; D045744:Cell Line, Tumor; D002999:Clone Cells; D018920:Coculture Techniques; D003432:Cross-Linking Reagents / Q000378:metabolism; D005786:Gene Expression Regulation / Q000276:immunology*; D006131:Growth Inhibitors / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D006801:Humans; D016130:Immunophenotyping; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology*; D014443:Tyrosine / Q000378:metabolism
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; C515070:CD300A protein, human; D003432:Cross-Linking Reagents; D006131:Growth Inhibitors; D011971:Receptors, Immunologic; D014443:Tyrosine; D000409:Alanine