The MHC class I binding proteins LIR-1 and LIR-2 inhibit Fc receptor-mediated signaling in monocytes.
The MHC class I binding proteins leukocyte immunoglobulin-like receptor (LIR)-1 and -2 recognize a similar broad spectrum of HLA-A, -B and -C alleles but are differentially expressed in lymphocytes, monocytes, and dendritic cells. In monocytes, phosphorylation of LIR-1 and LIR-2 results in the binding of the tyrosine phosphatase SHP-1. Coligation of either LIR with Fcgamma receptor I (CD64) inhibits tyrosine phosphorylation of the associated Fc receptor gamma chain and Syk molecules, as well as intracellular calcium mobilization. These findings suggest that LIR-1 and LIR-2 function as unique MHC class I receptors involved in the inhibition or down-modulation of monocyte activation signals, particularly those mediated through the receptors for IgG, IgE and IgA.
Fanger
N A
NA
Immunex Corporation, Seattle, Washington 98101, USA. nfanger@immunex.com
Cosman
D
D
Peterson
L
L
Braddy
S C
SC
Maliszewski
C R
CR
Borges
L
L
D000483:Alleles; D000818:Animals; D015703:Antigens, CD; D002118:Calcium / Q000378:metabolism; D006680:HLA Antigens / Q000235:genetics; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D000075362:Leukocyte Immunoglobulin-like Receptor B1; D009000:Monocytes / Q000502:physiology*; D010766:Phosphorylation; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases / Q000502:physiology; D011505:Protein-Tyrosine Kinases / Q000502:physiology; D011817:Rabbits; D011961:Receptors, Fc / Q000502:physiology*; D011971:Receptors, Immunologic / Q000502:physiology*
D015703:Antigens, CD; D006680:HLA Antigens; D047908:Intracellular Signaling Peptides and Proteins; C105299:LILRB1 protein, human; D000075362:Leukocyte Immunoglobulin-like Receptor B1; D011961:Receptors, Fc; D011971:Receptors, Immunologic; D011505:Protein-Tyrosine Kinases; C516724:PTPN11 protein, human; C509249:PTPN6 protein, human; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases; D002118:Calcium