Human cytomegalovirus, MHC class I and inhibitory signalling receptors: more questions than answers.
The human cytomegalovirus UL18 protein, an MHC class I homologue, has been shown to bind to leucocyte immunoglobulin-like receptor (LIR)-1, a member of a family of nine closely related immunoglobulin superfamily receptors expressed on leucocytes. The LIRs are related to the natural killer (NK)-cell immunoglobulin-like receptors and to several other immunoreceptors. Three groups of LIR molecules have been defined: those containing cytoplasmic domain inhibitory signalling motifs, those with short cytoplasmic domains and a charged residue within the transmembrane domain, and a secreted molecule. LIR-1 and LIR-2 bind to a broad spectrum of cellular MHC class I antigens, including HLA-A, -B and -C alleles. LIR-2 is expressed by all monocytes and dendritic cells, whereas LIR-1 is additionally expressed by B cells and subsets of T and NK cells. Upon tyrosine phosphorylation, LIR-1 and LIR-2 associate with the tyrosine phosphatase, SHP-1, and have been shown to inhibit Fc gamma RI signalling when co-crosslinked in monocytes. Evidence for and against a role of UL18 as an inhibitor of NK-cell function is discussed, as are possible functional outcomes of UL18-LIR-1 interactions in monocytic cells.
Immunex Corporation, Seattle, Washington 98110, USA. dcosman@immunex.com
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D000818:Animals; D015703:Antigens, CD; D002213:Capsid / Q000276:immunology*; D036022:Capsid Proteins; D003587:Cytomegalovirus / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D000075362:Leukocyte Immunoglobulin-like Receptor B1; D011971:Receptors, Immunologic / Q000276:immunology*; D011991:Receptors, Virus / Q000276:immunology*; D015398:Signal Transduction
D015703:Antigens, CD; D036022:Capsid Proteins; D015395:Histocompatibility Antigens Class I; C105299:LILRB1 protein, human; D000075362:Leukocyte Immunoglobulin-like Receptor B1; D011971:Receptors, Immunologic; D011991:Receptors, Virus; C079750:VP23 protein, Human herpesvirus 1