A NOVEL MHC CLASS-II EPITOPE EXPRESSED IN THYMIC MEDULLA BUT NOT CORTEX
A NOVEL MHC CLASS-II EPITOPE EXPRESSED IN THYMIC MEDULLA BUT NOT CORTEX
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DOI：
10.1038/338765a0
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发表时间：
1989-04-27
期刊：
影响因子：
64.8
通讯作者：
JANEWAY, CA
中科院分区：
文献类型：
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作者：
MURPHY, DB;LO, D;JANEWAY, CA
外周T细胞表达的受体是胸腺发育过程中发生的两个选择性事件的结果。正选择扩大了能够识别自身MHC分子提出的外源多肽的细胞，而负选择消除了细胞对自身MHC分子和相关的自肽1-4的反应。嵌合体研究表明，至少在识别MHC II类的T细胞中，与胸腺皮质上皮细胞的相互作用是导致前5种情况的原因，而来自骨髓的胸腺髓质细胞介导了后3、6-8。这种胸腺发育的观点得到了最近的形态计量分析的支持，表明在胸腺皮质中发现了自反应细胞，但在髓质中没有发现。尽管许多1-3、10-12的研究表明MHC-II类分子在这两个位点都有表达，但没有一项研究对观察到的T细胞的差异选择提供任何解释。在这里，我们描述了一种新的MHC II类表位，它存在于胸腺髓质细胞上，而不是皮质细胞上。该表位的抗体与B细胞上约10%的II类分子发生反应，可能识别自体多肽-MHC复合体。这些结果首次为不同组织中II类表位的差异表达提供了证据，并与不同的配体2，13-16，而不是同一配体17，18的不同亲和力阈值参与T细胞谱系的正和负选择的假设相一致。
THE repertoire of receptors expressed by peripheral T cells is the result of two selective events that occur during intrathymic development. Positive selection expands cells able to recognize foreign peptides presented by self MHC molecules, and negative selection eliminates cells reactive to self MHC molecules and associated self peptides1–4. Chimaera studies suggest that, at least in the case of T cells recognizing MHC class II, interaction with thymic cortical epithelial cells is responsible for the former5, whereas thymic medullary cells, of bone marrow origin, mediate the latter3, 6–8. This view of thymic development is supported by recent morphometric analyses9, showing that autoreactive cells are found in thymic cortex but not medulla. Although numerous1–3, 10–12studies have shown that MHC class II molecules are expressed in both sites, none provides any explanation for the differential selection of T cells that is observed. Here, we describe a novel MHC class II epitope which is found on cells in thymic medulla but not cortex. The antibody to this epitope reacts with about 10% of class II molecules on B cells and may be recognizing a self peptide–MHC complex. These results provide the first evidence for differential expression of class II epitopes in different tissues and are compatible with the hypothesis that different ligands2, 13–16, rather than different affinity thresholds for the same ligand17, 18, are involved in positive and negative selection of the T-cell repertoire.