Cosman D, Fanger N, Borges L
Immunex Corporation, Seattle, Washington 98110, USA.
Immunol Rev. 1999 Apr;168:177-85. doi: 10.1111/j.1600-065x.1999.tb01292.x.
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.
人巨细胞病毒UL18蛋白是一种MHC I类同源物，已被证明可与白细胞免疫球蛋白样受体（LIR）-1结合，LIR-1是在白细胞上表达的九个密切相关的免疫球蛋白超家族受体家族的成员之一。LIR与自然杀伤（NK）细胞免疫球蛋白样受体以及其他几种免疫受体相关。已定义了三组LIR分子：含有细胞质结构域抑制性信号基序的分子、具有短细胞质结构域且跨膜结构域内有一个带电荷残基的分子以及一种分泌分子。LIR-1和LIR-2可与多种细胞MHC I类抗原结合，包括HLA-A、-B和-C等位基因。所有单核细胞和树突状细胞均表达LIR-2，而B细胞以及T细胞和NK细胞亚群还额外表达LIR-1。酪氨酸磷酸化后，LIR-1和LIR-2与酪氨酸磷酸酶SHP-1结合，并且在单核细胞中共同交联时已被证明可抑制FcγRI信号传导。本文讨论了支持和反对UL18作为NK细胞功能抑制剂作用的证据，以及单核细胞中UL18-LIR-1相互作用可能的功能结果。
