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 recepto r(LIR)-1 and -2 recognize a similar broad spectrum of HLA-A, -B and -C alleles but are differentially expressed in lymphocytes, monocytes, a nd dendritic cells. In monocytes, phosphorylation of LIR-1 and LIR-2 r esults in the binding of the tyrosine phosphatase SHP-1. Coligation of either LIR with Fc gamma receptor I (CD64) inhibits tyrosine phosphor ylation of the associated Pc receptor gamma chain and Syk molecules, a s well as intracellular calcium mobilization. These findings suggest t hat LIR-1 and LIR-2 function as unique MHC class I receptors involved in the inhibition or down-modulation of monocyte activation signals, p articularly those mediated through the receptors for IgG, IgE and IgA.