The selection of M3-restricted T cells is dependent on M3 expression and presentation of N-formylated peptides in the thymus.
The selection of M3-restricted T cells is dependent on M3 expression and presentation of N-formylated peptides in the thymus.
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M3限制的T细胞的选择取决于M3表达和胸腺中N型甲基化肽的表现。
DOI：
10.1084/jem.190.12.1869
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发表时间：
1999-12-20
期刊：
影响因子：
--
通讯作者：
Wang CR
中科院分区：
文献类型：
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作者：
Chiu NM;Wang B;Kerksiek KM;Kurlander R;Pamer EG;Wang CR
主要组织相容性复合体（MHC）Ib类分子H2-M3结合来自线粒体和细菌的N-甲酰化肽。为了探索M3表达和肽供应在阳性和阴性选择中的作用，我们产生了转基因小鼠，所述转基因小鼠表达来自特异性针对肽（LemA）的CD8 + T细胞杂交瘤（D7）的M3限制性TCR-α/β。在β 2-微球蛋白缺陷和抗原处理相关转运蛋白（TAP）缺陷小鼠中，M3限制性转基因T细胞的发育受损，但H-2单倍型的变化不会减弱。胎儿胸腺器官培养物中M3/LemA特异性CD8+单阳性细胞的成熟对M3表达水平敏感，如通过抗体阻断和使用M3的castaneus突变等位基因所确定的。TAP −/−叶中的正选择被非激动剂线粒体和细菌肽拯救，而LemA和部分激动剂变体引起负选择。因此，M3限制性CD8 + T细胞被M3正向和负向选择，而没有来自更丰富的Ia类分子的贡献。这些结果表明，Ib类分子可以像Ia类分子一样在胸腺教育中发挥作用，尽管配体多样性有限且表达水平低。
The major histocompatibility complex (MHC) class Ib molecule H2-M3 binds N-formylated peptides from mitochondria and bacteria. To explore the role of M3 expression and peptide supply in positive and negative selection, we generated transgenic mice expressing an M3-restricted TCR-α/β from a CD8+ T cell hybridoma (D7) specific for a listerial peptide (LemA). Development of M3-restricted transgenic T cells is impaired in both β2-microglobulin–deficient and transporter associated with antigen processing (TAP)-deficient mice, but is not diminished by changes in the H-2 haplotype. Maturation of M3/LemA-specific CD8+ single positive cells in fetal thymic organ culture was sensitive to M3 expression levels as determined by antibody blocking and use of the castaneus mutant allele of M3. Positive selection was rescued in TAP−/− lobes by nonagonist mitochondrial and bacterial peptides, whereas LemA and a partial agonist variant caused negative selection. Thus, M3-restricted CD8+ T cells are positively and negatively selected by M3, with no contribution from the more abundant class Ia molecules. These results demonstrate that class Ib molecules can function in thymic education like class Ia molecules, despite limited ligand diversity and low levels of expression.