Dykstra M, Cherukuri A, Pierce S K
Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland 20852, USA.
J Leukoc Biol. 2001 Nov;70(5):699-707.
The multichain immune recognition receptors (MIRRs), including the T cell and B cell antigen receptors and the high affinity receptor for IgE, play an important role in immune cell signaling. The MIRRs have no inherent kinase activity, but rather associate with members of the Src-family kinases to initiate signaling. Although a great deal is understood about the biochemical cascades triggered by MIRRs, the mechanism by which signaling is initiated was not known. The evidence now indicates that the Src-family kinases are concentrated in cholesterol- and sphingolipid-rich membrane microdomains, termed lipid rafts, that exclude the MIRRs. Upon ligand-induced crosslinking the MIRRs translocate into rafts where they are phosphorylated. The MIRRs subsequently form highly ordered, polarized structures termed immunological synapses that provide for prolonged signaling. An understanding of the biochemical composition of rafts and synapses and the mechanisms by which these form should lend insight into the regulation of immune cell activation.
多链免疫识别受体（MIRRs），包括T细胞和B细胞抗原受体以及IgE高亲和力受体，在免疫细胞信号传导中发挥重要作用。MIRRs没有内在的激酶活性，而是与Src家族激酶成员结合以启动信号传导。尽管人们对MIRRs引发的生化级联反应了解很多，但信号传导起始的机制尚不清楚。现在有证据表明，Src家族激酶集中在富含胆固醇和鞘脂的膜微区，即所谓的脂筏中，而脂筏会排斥MIRRs。在配体诱导的交联作用下，MIRRs转移到脂筏中并在那里被磷酸化。MIRRs随后形成高度有序的极化结构，即免疫突触，从而实现延长的信号传导。了解脂筏和突触的生化组成以及它们形成的机制，应该有助于深入了解免疫细胞激活的调节。
