Human and mouse killer-cell inhibitory receptors recruit PTP1C and PTP1D protein tyrosine phosphatases.
NK cells express cell surface receptors for MHC class I proteins (KIR). Engagement of these receptors inhibits NK cell cytotoxic programs. KIR can be expressed on T cells, and their engagement also results in inhibition of effector functions initiated by the CD3/TCR complex. While human KIR genes belong to the Ig gene superfamily, mouse KIR belong to a family of dimeric lectins. Despite these distinct evolutionary origins, we show here that both HLA-Cw3-specific human p58.183 receptors and H-2D d/k-specific mouse Ly49A receptors recruit the same protein tyrosine phosphatases, PTP1C and PTP1D, upon phosphorylation of critical intracytoplasmic tyrosine residues. These results document a common pathway by which diverse KIR can down-regulate NK and T cell activation programs, and further define the sequence of the immunoreceptor tyrosine-based inhibitory motif (ITIM), initially described in FcgammaRIIB1, and expressed in both human and mouse KIR.
Olcese
L
L
Center for Immunology, INSERM/CNRS of Marseille-Luminy, France.
Lang
P
P
Vély
F
F
Cambiaggi
A
A
Marguet
D
D
Bléry
M
M
Hippen
K L
KL
Biassoni
R
R
Moretta
A
A
Moretta
L
L
Cambier
J C
JC
Vivier
E
E
D000595:Amino Acid Sequence; D000818:Animals; D006801:Humans; D007694:Killer Cells, Natural / Q000201:enzymology / Q000502:physiology*; D008213:Lymphocyte Activation; D051379:Mice; D008969:Molecular Sequence Data; D010748:Phosphopeptides / Q000378:metabolism; D019000:Phosphotyrosine / Q000378:metabolism; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000502:physiology*; D015398:Signal Transduction
D010748:Phosphopeptides; D011971:Receptors, Immunologic; D019000:Phosphotyrosine; D017027:Protein Tyrosine Phosphatases