Hutchinson M J, Harrison P T, Floto R A, Allen J M
Division of Biochemistry and Molecular Biology, University of Glasgow.
Eur J Immunol. 1995 Feb;25(2):481-7. doi: 10.1002/eji.1830250226.
Receptors for the invariant chain of immunoglobulins (FcR) define the cellular response to specific antigens. Fc gamma R recognize IgG and so elicit a variety of effector functions including phagocytosis. We are interested in the structural determinants for Fc gamma R-mediated phagocytosis, specifically Fc gamma RI(p135) and Fc gamma RIIa isoforms. The low-affinity receptor, Fc gamma RIIa, is found on macrophages and its cytoplasmic domain contains a tyrosine activation motif which has previously been shown to regulate endocytosis. In contrast, Fc gamma RI has no known signaling motifs, though a functional interaction has recently been demonstrated with the gamma chain of the high-affinity receptor for IgE, Fc epsilon RI. This accessory molecule has a cytoplasmic tyrosine activation motif implicated in signal transduction. Here we demonstrate that although Fc gamma RI transiently expressed on COS-7 cells is able to rosette opsonized SRBC, it cannot phagocytose them. If the cytoplasmic domain of either gamma chain or Fc gamma RIIa replaces that of Fc gamma RI in a chimeric receptor, efficient phagocytosis occurs. This particle ingestion is sensitive to the tyrosine kinase inhibitor genistein. Chimeric receptors where the extracellular domain of either Fc gamma RI or Fc gamma RIIa is replaced with that of CD2, a T cell antigen, indicate that Fc gamma R-mediated phagocytosis is ligand independent. We conclude that phagocytosis is dependent upon close particle apposition, tyrosine kinase activity, and that the process is ligand independent.
免疫球蛋白恒定链受体（FcR）决定了细胞对特定抗原的反应。FcγR识别IgG，从而引发包括吞噬作用在内的多种效应功能。我们对FcγR介导的吞噬作用的结构决定因素感兴趣，特别是FcγRI（p135）和FcγRIIa亚型。低亲和力受体FcγRIIa存在于巨噬细胞上，其胞质结构域含有一个酪氨酸激活基序，此前已证明该基序可调节内吞作用。相比之下，FcγRI没有已知的信号基序，尽管最近已证明它与IgE高亲和力受体FcεRI的γ链存在功能相互作用。这种辅助分子有一个参与信号转导的胞质酪氨酸激活基序。在这里，我们证明，虽然在COS-7细胞上瞬时表达的FcγRI能够与调理的SRBC形成玫瑰花结，但它不能吞噬它们。如果在嵌合受体中，γ链或FcγRIIa的胞质结构域取代FcγRI的胞质结构域，就会发生有效的吞噬作用。这种颗粒摄取对酪氨酸激酶抑制剂染料木黄酮敏感。用T细胞抗原CD2的胞外结构域取代FcγRI或FcγRIIa的胞外结构域的嵌合受体表明，FcγR介导的吞噬作用不依赖配体。我们得出结论，吞噬作用依赖于颗粒的紧密附着、酪氨酸激酶活性，并且该过程不依赖配体。
