Correlation between CD8 dependency and determinant density using peptide-induced, Ld-restricted cytotoxic T lymphocytes
Correlation between CD8 dependency and determinant density using peptide-induced, Ld-restricted cytotoxic T lymphocytes
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使用肽诱导的 Ld 限制性细胞毒性 T 淋巴细胞研究 CD8 依赖性和决定簇密度之间的相关性
DOI：
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发表时间：
1991
影响因子：
15.3
通讯作者：
J. Connolly
中科院分区：
文献类型：
--
作者：
M. A. Alexander;C. A. Damico;K. Wieties;T. Hansen;J. Connolly
我们利用H-2Ld的一些独特性质来研究细胞毒性T淋巴细胞（CTL）启动与效应功能的决定簇密度要求，并将决定簇密度要求与CD 8依赖性相关联。在以前的研究中（Lie，W.- R.，N. B。Myers，J. Gorka，R. J. Rubocki，J. M. Connolly和T. H.汉森。1990.自然[伦敦]。344：439），我们证明了用已知受H-2Ld限制的肽培养正常细胞导致表面Ld表达增加2至4倍。在本研究中，我们证明了通过用鼠巨细胞病毒或tum-肽以先前显示的导致最大诱导Ld表达的浓度培养脾细胞来产生Ld限制性的肽特异性体外原代CTL。靶细胞可以用比初级致敏所需剂量更低的肽来致敏这些CTL的识别。这证明了启动与效应子功能的决定簇密度要求的差异。用肽产生的体外原代CTL可弱裂解内源性表达该决定子的靶细胞，并且容易获得能够强裂解内源性表达子的CTL系和克隆。在这两种情况下，用外源肽处理的靶细胞比内源性表达抗原的靶细胞更好地溶解。这表明肽补料与内源性靶标的决定簇密度存在差异。当观察到表达内源性决定簇的靶细胞的裂解水平与使靶敏感以被各种tum-特异性CTL克隆识别所需的肽的量成反比时，这种解释得到了证实。此外，用于处理靶细胞的肽和CD 8抗体的同时滴定揭示了所分析的各种CTL克隆显示出广泛不同的CD 8依赖性。在每种情况下，CD 8依赖性与决定簇密度要求呈负相关。因此，CTL的CD 8依赖性是相对的，但与它们对决定簇密度的依赖性显示出绝对和定量的相关性。这些发现表明，在生理条件下，只有低决定簇密度可能会遇到，所有的CTL克隆将显示至少部分的CD 8依赖性。
We have taken advantage of some unique properties of H-2Ld to investigate the determinant density requirements for cytotoxic T lymphocyte (CTL) priming versus effector function and to correlate the determinant density requirements with CD8 dependency. In a previous study (Lie, W.-R., N. B. Myers, J. Gorka, R. J. Rubocki, J. M. Connolly, and T. H. Hansen. 1990. Nature [Lond.]. 344:439), we demonstrated that culturing normal cells with peptides known to be restricted by H-2Ld led to a two- to fourfold increase in surface Ld expression. In the present study, we demonstrate the generation of Ld- restricted, peptide-specific in vitro primary CTL by culturing spleen cells with murine cytomegalovirus or tum- peptide at concentrations previously shown to result in maximum induction of Ld expression. Target cells can be sensitized for recognition by these CTL with lower dose of peptide than are required for the primary sensitization. This demonstrates differences in the determinant density requirements for priming versus effector function. The in vitro primary CTL generated with peptide can weakly lyse target cells that express the determinant endogenously, and CTL lines and clones capable of strong lysis of endogenous expressors are easily obtained. In both cases, target cells treated with exogenous peptide are lysed better than target cells expressing antigen endogenously. This suggested that there are differences in the determinant density of peptide-fed versus endogenous targets. This interpretation was substantiated when it was observed that the level of lysis of target cells expressing endogenous determinants correlated inversely with the amount of peptide required to sensitize targets for recognition by various tum- -specific CTL clones. Furthermore, simultaneous titration of both the peptide used to treat target cells and the antibody to CD8 revealed that the various CTL clones analyzed displayed widely disparate CD8 dependencies. In each case, the CD8 dependency correlated inversely with the determinant density requirement. Therefore, CD8 dependency of CTL is relative, but shows an absolute and quantitative correlation with their dependency on determinant density. These findings suggest that under physiologic conditions, where only low determinant densities are likely to be encountered, all CTL clones will show at least partial CD8 dependency.
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DOI：
10.1073/pnas.84.13.4562
发表时间：
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影响因子：
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DOI：
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发表时间：
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Journal of immunology (Baltimore, Md. : 1950)
影响因子：
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DOI：
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发表时间：
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期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
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