Cutting Edge: LFA-1 Integrin-Dependent T Cell Adhesion Is Regulated by Both Ag Specificity and Sensitivity1
Cutting Edge: LFA-1 Integrin-Dependent T Cell Adhesion Is Regulated by Both Ag Specificity and Sensitivity1
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最前沿：LFA-1 整合素依赖性 T 细胞粘附受 Ag 特异性和敏感性调节1
作者：
Kristen L. Mueller;M. Daniels;A. Felthauser;Charlly Kao;S. Jameson;Y. Shimizu
TCR的Ab刺激快速增强LFA-1整联蛋白的功能活性。尽管TCR介导的LFA-1活性变化被认为促进T细胞-APC相互作用，但TCR介导的LFA-1触发的Ag特异性和敏感性尚不清楚。我们证明肽/MHC（pMHC）四聚体快速增强OT-I TCR转基因CD 8 + T细胞对纯化的ICAM-1的LFA-1依赖性粘附。src家族酪氨酸激酶或PI 3 K活性的抑制阻断了pMHC四聚体和抗CD 3刺激的粘附。这些作用是高度特异性的，因为部分激动剂和拮抗剂pMHC四聚体不能刺激OT-I T细胞粘附于ICAM-1。T细胞粘附至ICAM-1所需的Ag阈值类似于早期T细胞活化事件的Ag阈值，因为最佳LFA-1活化发生在不能诱导最大T细胞增殖的四聚体浓度下。因此，TCR信号传导至LFA-1是高度Ag特异性的，并且对低浓度的Ag敏感。
Ab stimulation of the TCR rapidly enhances the functional activity of the LFA-1 integrin. Although TCR-mediated changes in LFA-1 activity are thought to promote T cell-APC interactions, the Ag specificity and sensitivity of TCR-mediated triggering of LFA-1 is not clear. We demonstrate that peptide/MHC (pMHC) tetramers rapidly enhance LFA-1-dependent adhesion of OT-I TCR transgenic CD8+ T cells to purified ICAM-1. Inhibition of src family tyrosine kinase or PI3K activity blocked pMHC tetramer- and anti-CD3-stimulated adhesion. These effects are highly specific because partial agonist and antagonist pMHC tetramers are unable to stimulate OT-I T cell adhesion to ICAM-1. The Ag thresholds required for T cell adhesion to ICAM-1 resemble those of early T cell activation events, because optimal LFA-1 activation occurs at tetramer concentrations that fail to induce maximal T cell proliferation. Thus, TCR signaling to LFA-1 is highly Ag specific and sensitive to low concentrations of Ag.
最前沿：TCR 拮抗作用的主要负信号模型的测试。
DOI：
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发表时间：
1999
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
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作者：
Daniels,MA;Schober,SL;Hogquist,KA;Jameson,SC
通讯作者：
Jameson,SC
影响因子：
32.4
作者：
Busch, DH;Pilip, IM;Pamer, EG
通讯作者：
Pamer, EG