Positive selection of CD8+ T cells induced by major histocompatibility complex binding peptides in fetal thymic organ culture.
Positive selection of CD8+ T cells induced by major histocompatibility complex binding peptides in fetal thymic organ culture.
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DOI：
10.1084/jem.177.5.1469
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发表时间：
1993-05-01
期刊：
影响因子：
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通讯作者：
Bevan MJ
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文献类型：
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作者：
Hogquist KA;Gavin MA;Bevan MJ
我们用体外系统研究了主要组织相容性复合体I类结合肽对胸腺发育的影响。将ⅰ类轻链（β 2微球蛋白或β 2 M-/-）缺失小鼠的胎胸腺叶体外培养10 d，在此期间T细胞前体发育为成熟的T细胞。在这些器官培养中，如在成年或新生儿的β 2 M-/-胸腺中，CD8+成熟T细胞没有发育，这表明在早期小鼠胸腺发育过程中看到的成熟T细胞是阳性选择过程的结果。在这些培养物中，我们添加了各种I类结合肽，有或没有外源性β 2M来源。CD8+ T细胞仅在β 2M和多肽存在的情况下才有不同程度的发育。使用不同复杂程度的多肽混合物，我们发现这一过程的效率更多地取决于多肽的复杂性而不是多肽的浓度。这些数据证明了多肽在积极选择过程中的特定作用。此外，该培养系统应该有助于鉴定肽，这些肽可以促进TCR转基因小鼠中表达特定T细胞受体（TCR）的细胞的阳性选择。
We have used an in vitro system to study the effects of major histocompatibility complex class I binding peptides on thymic development. Fetal thymus lobes from mice deficient in the class I light chain (beta 2 microglobulin or beta 2 M-/-) were cultured for 10 d in vitro, during which time T cell precursors develop into mature T cells. In these organ cultures, as in the adult or neonatal beta 2 M-/- thymus, CD8+ mature T cells did not develop, demonstrating that the mature T cells seen during early murine thymic development are the result of the positive selection process. To these cultures we added various class I binding peptides with or without a source of exogenous beta 2M. CD8+ T cells developed to various degrees only in the presence of beta 2M and peptides. Using peptide mixtures of differing complexity, we showed that the efficiency of this process is dependent more on peptide complexity than on peptide concentration. These data argue for a specific role for peptides in the process of positive selection. Furthermore, this culture system should be useful in identifying peptides that can promote positive selection of cells expressing a specific T cell receptor (TCR) in TCR transgenic mice.