Hogquist K A, Jameson S C, Heath W R, Howard J L, Bevan M J, Carbone F R
Howard Hughes Medical Institute, Department of Immunology, University of Washington, Seattle 98195.
Cell. 1994 Jan 14;76(1):17-27. doi: 10.1016/0092-8674(94)90169-4.
We have used organ culture of fetal thymic lobes from T cell receptor (TCR) transgenic beta 2M(-/-) mice to study the role of peptides in positive selection. The TCR used was from a CD8+ T cell specific for ovalbumin 257-264 in the context of Kb. Several peptides with the ability to induce positive selection were identified. These peptide-selected thymocytes have the same phenotype as mature CD8+ T cells and can respond to antigen. Those peptides with the ability to induce positive selection were all variants of the antigenic peptide and were identified as TCR antagonist peptides for this receptor. One peptide tested, E1, induced positive selection on the beta 2M(-/-) background but negative selection on the beta 2M(+/-) background. These results show that the process of positive selection is exquisitely peptide specific and sensitive to extremely low ligand density and support the notion that low efficacy ligands mediate positive selection.
我们利用来自T细胞受体（TCR）转基因β2M（-/-）小鼠的胎儿胸腺叶器官培养物来研究肽在阳性选择中的作用。所使用的TCR来自在Kb背景下对卵清蛋白257-264特异的CD8 + T细胞。鉴定出了几种具有诱导阳性选择能力的肽。这些经肽选择的胸腺细胞具有与成熟CD8 + T细胞相同的表型，并且能够对抗原作出反应。那些具有诱导阳性选择能力的肽都是抗原肽的变体，并被鉴定为该受体的TCR拮抗剂肽。所测试的一种肽E1，在β2M（-/-）背景上诱导阳性选择，但在β2M（+/-）背景上诱导阴性选择。这些结果表明，阳性选择过程对肽具有高度特异性，并且对极低的配体密度敏感，支持低效能配体介导阳性选择的观点。
