The MHC class I binding proteins LIR‐1 and LIR‐2 inhibit Fc receptor‐mediated signaling in monocytes

• Published in: European journal of immunology 1998-11, Vol.28 (11), p.3423-3434
• Main Authors: Fanger, Neil A., Cosman, David, Peterson, Lori, Braddy, Steven C., Maliszewski, Charles R., Borges, Luis
• Format: Article
• Language: English
• Subjects: Alleles; Animals; Antigens, CD; Calcium - metabolism; Fc receptor; HLA Antigens - genetics; Humans; Intracellular Signaling Peptides and Proteins; Leukocyte Immunoglobulin-like Receptor B1; Leukocyte immunoglobulin‐like receptor; LIR; MHC class I; Monocyte; Monocytes - physiology; Phosphorylation; Protein Tyrosine Phosphatase, Non-Receptor Type 11; Protein Tyrosine Phosphatase, Non-Receptor Type 6; Protein Tyrosine Phosphatases - physiology; Protein-Tyrosine Kinases - physiology; Rabbits; Receptors, Fc - physiology; Receptors, Immunologic - physiology
• ISSN: 0014-2980; 1521-4141
• DOI: 10.1002/(SICI)1521-4141(199811)28:11<3423::AID-IMMU3423>3.0.CO;2-2

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 Fcγ receptor I (CD64) inhibits tyrosine phosphorylation of the associated Fc receptor γ 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.