Spain L M, Jorgensen J L, Davis M M, Berg L J
Department of Cellular and Developmental Biology, Harvard University, Cambridge, MA 02138.
J Immunol. 1994 Feb 15;152(4):1709-17.
The developmental fate of an immature T cell is determined in the thymus. Depending on the specificity of its TCR, a thymocyte receives signals to either die or differentiate. We have used fetal thymic organ cultures derived from TCR transgenic mice to examine the role of MHC/peptide ligands in T cell selection. Single amino acid substituted peptide analogues of the Ag recognized by the transgenic TCR were examined for their ability to enhance or interfere with positive selection. We have identified a nonstimulatory peptide analogue that interferes with the differentiation of transgenic CD4+8+ thymocytes into CD4+8- cells. We also show that this peptide, substituted in a TCR contact residue, is a competitive antagonist for activation of the T cell hybridoma expressing the same TCR. These observations demonstrate a novel mechanism for tolerance induction in the thymus.
未成熟T细胞的发育命运在胸腺中决定。胸腺细胞根据其TCR的特异性接收信号，要么死亡，要么分化。我们利用源自TCR转基因小鼠的胎儿胸腺器官培养物来研究MHC/肽配体在T细胞选择中的作用。检测了转基因TCR识别的抗原的单氨基酸取代肽类似物增强或干扰阳性选择的能力。我们鉴定出一种非刺激性肽类似物，它干扰转基因CD4+8+胸腺细胞分化为CD4+8-细胞。我们还表明，这种在TCR接触残基处被取代的肽是表达相同TCR的T细胞杂交瘤激活的竞争性拮抗剂。这些观察结果证明了胸腺中诱导耐受的一种新机制。
