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首页> 外文期刊>Cellular immunology >Major histocompatibility complex class I restricted T-cell autoreactivity in human peripheral blood mononuclear cells.
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Major histocompatibility complex class I restricted T-cell autoreactivity in human peripheral blood mononuclear cells.

机译：主要的组织相容性复合体I类限制了人类外周血单核细胞中的T细胞自身反应性。

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During selection in the thymus or any subsequent response, T-cells recognize peptides bound to major histocompatibility complex (MHC) molecules. Peptides produced by lysosomes or by proteasome/immunoproteasome stimulate CD4+ or CD8+ T-cell, respectively. Inflammation alters components of both antigen-processing pathways resulting in the production of different peptides. The role of such changes in selfon-self discrimination was examined in autologous mixed peripheral blood mononuclear cell cultures. Stimulator cells were incubated in the presence or absence of INF-gamma, with or without lysosome inhibitors (ammonium chloride/chloroquine), cathepsin inhibitor (E-64), or proteasome/immunoproteasome inhibitor (epoxomicin). Responder cells were added and zeta-chain phosphorylated forms were used as read out. INF-gamma did not affect zeta-chain phosphorylated forms, which means that the expected INF-gamma induced alterations in antigen processing machinery do not influence selfon-self discrimination. Surprisingly, the completely phosphorylated 23-kDa zeta-chain was always present except in the case of epoxomicin, indicating the presence of MHC class I restricted autoreactive CD8+ T-cells but not of MHC class II restricted autoreactive CD4+ T-cells, possibly due to more efficient negative selection in the thymus of the latter. Autoimmunity is prevented due to absence of help by CD4+ T-cells. This conclusion was confirmed by the lack of differences in IL-2 levels in cell culture supernatants, as well as, by the absence of differences in cell proliferation under the various conditions described above.
机译：在胸腺选择或任何后续反应期间，T细胞识别与主要组织相容性复合物（MHC）分子结合的肽。溶酶体或蛋白酶体/免疫蛋白酶体产生的肽分别刺激CD4 +或CD8 + T细胞。炎症改变了两种抗原加工途径的成分，导致产生不同的肽。在自体混合外周血单核细胞培养物中检查了这种变化在自我/非自我辨别中的作用。在存在或不存在INF-γ的情况下，在有或没有溶酶体抑制剂（氯化铵/氯喹），组织蛋白酶抑制剂（E-64）或蛋白酶体/免疫蛋白酶体抑制剂（环氧霉素）下孵育刺激细胞。添加响应细胞，并使用zeta链磷酸化形式读出。 INF-γ不会影响Zeta链的磷酸化形式，这意味着预期INF-γ诱导的抗原加工机制改变不会影响自我/非自我区分。出人意料的是，除了埃博霉素外，总是存在完全磷酸化的23 kDaζ链，这表明存在MHC I类限制性自身反应性CD8 + T细胞，但不存在MHC II类限制性自身反应性CD4 + T细胞，可能是由于后者的胸腺中更有效的否定选择。由于缺乏CD4 + T细胞的帮助，因此可以预防自身免疫。通过在细胞培养上清液中IL-2水平的差异的缺乏以及在上述各种条件下细胞增殖的差异的存在，可以证实该结论。

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