A role for CD8 in the developmental tuning of antigen recognition and CD3 conformational change
A role for CD8 in the developmental tuning of antigen recognition and CD3 conformational change
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DOI：
10.4049/jimmunol.180.6.3900
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发表时间：
2008-03-15
影响因子：
4.4
通讯作者：
Palmer, Ed
中科院分区：
文献类型：
--
作者：
Gil, Diana;Schrum, Adam G.;Palmer, Ed
通过肽-MHC I类（pMHC）配体的TCR接合诱导有助于T细胞信号传导的CD 3（CD 3 Δ c）中的构象变化（Δ c）。我们发现，当这种相互作用发生在原代T细胞和APC之间时，需要CD 8辅助受体来产生CD 3 Δ c。有趣的是，无论是增强Ag结合强度，也没有Src激酶信号解释这种辅助受体活性。此外，Ag诱导的CD 3 δ c通过伴随T细胞成熟并限制CD 8活性的唾液酸化的增加而在发育上减弱。因此，弱配体和强配体均诱导预选胸腺细胞中的CD 3 δ c，但只有强配体在成熟T细胞中有效。我们提出，CD 8参与TCR/pMHC相互作用可以通过将生产性Ag从TCR“翻译”到CD 3复合物来物理调节CD 3 Δ c诱导。这表明了一种机制，通过该机制，CD 8唾液酸化的发育调节变化可能有助于T细胞敏感性的发育调节。
TCR engagement by peptide-MHC class I (pMHC) ligands induces a conformational change (Delta c) in CD3 (CD3 Delta c) that contributes to T cell signaling. We found that when this interaction took place between primary T lineage cells and APCs, the CD8 coreceptor was required to generate CD3 Delta c. Interestingly, neither enhancement of Ag binding strength nor Src kinase signaling explained this coreceptor activity. Furthermore, Ag-induced CD3 Delta c was developmentally attenuated by the increase in sialylation that accompanies T cell maturation and limits CD8 activity. Thus, both weak and strong ligands induced CD3 Delta c in preselection thymocytes, but only strong ligands were effective in mature T cells. We propose that CD8 participation in the TCR/pMHC interaction can physically regulate CD3 Delta c induction by "translating" productive Ag encounter from the TCR to the CD3 complex. This suggests one mechanism by which the developmentally regulated variation in CD8 sialylation may contribute to the developmental tuning of T cell sensitivity.