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Dynamics of the Coreceptor-LCK Interactions during T Cell Development Shape the Self-Reactivity of Peripheral CD4 and CD8 T Cells.
Cell Reports ( IF 7.5 ) Pub Date : 2020-02-04 , DOI: 10.1016/j.celrep.2020.01.008 Veronika Horkova 1 , Ales Drobek 1 , Daniel Mueller 2 , Celine Gubser 3 , Veronika Niederlova 1 , Lena Wyss 4 , Carolyn G King 2 , Dietmar Zehn 5 , Ondrej Stepanek 1
Cell Reports ( IF 7.5 ) Pub Date : 2020-02-04 , DOI: 10.1016/j.celrep.2020.01.008 Veronika Horkova 1 , Ales Drobek 1 , Daniel Mueller 2 , Celine Gubser 3 , Veronika Niederlova 1 , Lena Wyss 4 , Carolyn G King 2 , Dietmar Zehn 5 , Ondrej Stepanek 1
Affiliation
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Overtly self-reactive T cells are removed during thymic selection. However, it has been recently established that T cell self-reactivity promotes protective immune responses. Apparently, the level of self-reactivity of mature T cells must be tightly balanced. Our mathematical model and experimental data show that the dynamic regulation of CD4- and CD8-LCK coupling establish the self-reactivity of the peripheral T cell pool. The stoichiometry of the interaction between CD8 and LCK, but not between CD4 and LCK, substantially increases upon T cell maturation. As a result, peripheral CD8+ T cells are more self-reactive than CD4+ T cells. The different levels of self-reactivity of mature CD8+ and CD4+ T cells likely reflect the unique roles of these subsets in immunity. These results indicate that the evolutionary selection pressure tuned the CD4-LCK and CD8-LCK stoichiometries, as they represent the unique parts of the proximal T cell receptor (TCR) signaling pathway, which differ between CD4+ and CD8+ T cells.
中文翻译：
T细胞发育过程中，Coreceptor-LCK相互作用的动力学决定了外周CD4和CD8 T细胞的自反应性。
在胸腺选择过程中，会清除明显的自我反应性T细胞。然而，最近已经确定，T细胞自身反应性促进保护性免疫应答。显然，必须紧密平衡成熟T细胞的自我反应水平。我们的数学模型和实验数据表明，CD4-和CD8-LCK偶联的动态调节建立了外周T细胞池的自反应性。T细胞成熟时，CD8与LCK之间相互作用的化学计量比，而不是CD4与LCK之间相互作用的化学计量比显着提高。结果，外周CD8 + T细胞比CD4 + T细胞更具自反应性。成熟的CD8 +和CD4 + T细胞的自我反应水平不同，可能反映了这些亚群在免疫中的独特作用。
更新日期：2020-02-04
中文翻译：
T细胞发育过程中，Coreceptor-LCK相互作用的动力学决定了外周CD4和CD8 T细胞的自反应性。
在胸腺选择过程中，会清除明显的自我反应性T细胞。然而，最近已经确定，T细胞自身反应性促进保护性免疫应答。显然，必须紧密平衡成熟T细胞的自我反应水平。我们的数学模型和实验数据表明，CD4-和CD8-LCK偶联的动态调节建立了外周T细胞池的自反应性。T细胞成熟时，CD8与LCK之间相互作用的化学计量比，而不是CD4与LCK之间相互作用的化学计量比显着提高。结果，外周CD8 + T细胞比CD4 + T细胞更具自反应性。成熟的CD8 +和CD4 + T细胞的自我反应水平不同，可能反映了这些亚群在免疫中的独特作用。
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