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首页> 外文期刊>Infection and immunity >A mutation of F47 to A in staphylococcus enterotoxin A activates the T-cell receptor Vbeta repertoire in vivo.
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A mutation of F47 to A in staphylococcus enterotoxin A activates the T-cell receptor Vbeta repertoire in vivo.

机译：金黄色葡萄球菌肠毒素A中的F47突变为A，可在体内激活T细胞受体Vbeta库。

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The bacterial superantigen staphylococcal enterotoxin A (SEA) binds with high affinity to major histocompatibility complex (MHC) class II molecules and subsequently activates T cells bearing particular T-cell receptor (TCR) Vbeta chains. Structural and mutational studies have defined two distinct MHC class II binding sites located in the N-terminal and C-terminal domains of SEA. The N-terminal F47 amino acid is critically involved in a low-affinity interaction to the MHC class II alpha-chain, while the C-terminal residues H187, H225, and D227 coordinate a Zn2+ ion and bind with moderate affinity to the beta-chain. In order to analyze whether the SEA-MHC class II alpha-chain interaction plays a role in dictating the in vivo repertoire of T-cell subsets, we studied distinct Vbeta populations after stimulation with wild-type SEA [SEA(wt)] and SEA with an F47A mutation [SEA(F47A)]. Injections of SEA(wt) in C57BL/6 mice induced cytokine release in serum, strong cytotoxic T-lymphocyte activity, expansion of T-cell subsets, and modulated expression of the T-cell activation antigens CD25, CD11a, CD44, CD62L, and CD69. SEA-reactive TCR Vbeta3+ and Vbeta11+ T cells were activated, while TCR Vbeta8+ T cells remained unaffected. The SEA(F47A) mutant protein induced a weaker T-cell response and failed to induce substantial interleukin-6 production compared to SEA(wt). Notably, SEA(F47A) failed to activate TCR Vbeta11+ T cells, whereas in vivo expansion and modulation of T-cell activation markers on TCR Vbeta3+ T cells were similar to those for SEA(wt). A similar response to SEA(F47A) was seen among CD4+ and CD8+ T cells. Activation of TCR Vbeta3+ and TCR Vbeta11+ T-cell hybridomas confirmed that SEA(F47A) activates TCR Vbeta3+ but not TCR Vbeta11+ T cells. The data support the view that the SEA-N-terminal MHC class II alpha-chain interaction defines a topology that is required for engagement of certain TCR Vbeta chains in vivo.
机译：细菌超抗原葡萄球菌肠毒素A（SEA）与主要组织相容性复合体（MHC）II类分子高亲和力结合，随后激活带有特定T细胞受体（TCR）Vbeta链的T细胞。结构和突变研究已定义了两个不同的II类MHC II类结合位点，位于SEA的N端和C端域。 N端F47氨基酸关键参与与MHC II类α链的低亲和力相互作用，而C端残基H187，H225和D227协调Zn2 +离子并以适度亲和力与β-链。为了分析SEA-MHC II类α链相互作用是否在决定T细胞亚群的体内组成中起作用，我们研究了野生型SEA [SEA（wt）]和SEA刺激后不同的Vbeta群体具有F47A突变[SEA（F47A）]。在C57BL / 6小鼠中注射SEA（wt）会诱导血清中的细胞因子释放，强大的细胞毒性T淋巴细胞活性，T细胞亚群的扩展以及T细胞活化抗原CD25，CD11a，CD44，CD62L和CD69。 SEA反应性TCR Vbeta3 +和Vbeta11 + T细胞被激活，而TCR Vbeta8 + T细胞保持不受影响。与SEA（wt）相比，SEA（F47A）突变蛋白诱导了较弱的T细胞反应，并且未能诱导大量白介素6的产生。值得注意的是，SEA（F47A）无法激活TCR Vbeta11 + T细胞，而TCR Vbeta3 + T细胞上T细胞激活标记的体内扩增和调节与SEA（wt）相似。在CD4 +和CD8 + T细胞中发现了对SEA（F47A）的类似反应。 TCR Vbeta3 +和TCR Vbeta11 + T细胞杂交瘤的激活证实SEA（F47A）激活TCR Vbeta3 +，但不激活TCR Vbeta11 + T细胞。数据支持这样的观点，即SEA-N端MHC II类α链相互作用定义了体内某些TCR Vbeta链参与所需要的拓扑。

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