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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Class I negative CD8 T cells reveal the confounding role of peptide-transfer onto CD8 T cells stimulated with soluble H2-K~b molecules
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Class I negative CD8 T cells reveal the confounding role of peptide-transfer onto CD8 T cells stimulated with soluble H2-K~b molecules

机译:I类CD8 T阴性细胞揭示了肽转移到可溶性H2-K〜b分子刺激的CD8 T细胞上的混杂作用

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摘要

Crosslinking of the T cell receptor has been proposed to be a prerequisite for T cell activation. Although the evidence supports this notion for CD4 T cells, the situation for CD8 T cells is less clear. Soluble class I monomers have been used to determine activation requirements in vitro with contradictory results. The possibility of transfer of peptide from soluble class I molecules onto class I molecules present on the surface of CD8 T cells, with ensuing presentation to other CD8 T cells, has been widely ignored. We show that monomeric and tetrameric class I molecules as well as free peptide can stimulate naive CD8 T cells in vitro. We generate and characterize CD8 T cells that express the OT-I T cell receptor (for K~b/SIINFEKL) yet lack K~b and D~b molecules, and show that their activation requirements differ from their class I positive counterparts when stimulated with soluble K~b molecules. By eliminating the confounding effect of peptide transfer, we unmask the true activation requirements for naieve CD8 T cells and show that multivalent engagement of T cell receptors, as well as costimula-tion, is required for optimal stimulation.
机译:已经提出T细胞受体的交联是T细胞活化的先决条件。尽管证据支持CD4 T细胞的这一观点,但CD8 T细胞的情况尚不清楚。可溶性I类单体已用于确定体外活化要求,但结果相反。肽从可溶性I类分子转移到CD8 T细胞表面上存在的I类分子上的可能性,并随后呈现给其他CD8 T细胞,这一可能性已被广泛忽略。我们显示,单体和四聚体的I类分子以及游离肽可以在体外刺激幼稚的CD8 T细胞。我们生成并表征了表达OT-I T细胞受体(对于K〜b / SIINFEKL)但缺乏K〜b和D〜b分子的CD8 T细胞,并显示了它们的激活要求在被刺激时不同于其I类阳性对应物具有可溶的K〜b分子通过消除肽转移的混杂效应,我们揭示了天然CD8 T细胞的真正激活要求,并表明T细胞受体的多价结合以及共刺激是最佳刺激所必需的。

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