Cognate peptides induce self-destruction of CD8+ cytolytic T lymphocytes.
Cognate peptides induce self-destruction of CD8+ cytolytic T lymphocytes.
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DOI：
10.1073/pnas.87.22.9015
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发表时间：
1990-11
影响因子：
11.1
通讯作者：
P. Walden;H. Eisen
中科院分区：
文献类型：
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作者：
P. Walden;H. Eisen
细胞毒性T淋巴细胞（ctl）已被证明相对抵抗其他ctl的细胞溶解攻击。然而，我们在这里表明，克隆的ctl，在没有其他细胞的情况下，暴露于它们的同源肽（定义为与主要组织相容性复合体蛋白相关的那些，被T细胞的抗原特异性受体识别）会被破坏。破坏与肽浓度成正比，可以通过与同源肽竞争的第二肽来防止，该肽与ctl的I类主要组织相容性复合体蛋白竞争。肽诱导的ctl外观变化的速度和程度表明，这种破坏可能主要是由于单个ctl的自我识别和自我破坏（自杀），而不是由于同一培养中同一克隆的其他ctl的破坏（自相残杀）。这种效应也可能发生在体内，因为在适当的时间将同源肽注射到卵清蛋白免疫的小鼠中，似乎会耗尽其脾脏中引物的抗卵清蛋白ctl。结果指出了胸腺后细胞溶解T细胞消除的一种可能的生理机制，这些细胞识别与自身主要组织相容性复合物蛋白相关的自身肽。这一结果也提高了同源肽可能最终被证明在治疗上对消除引起病理性细胞破坏的CTL克隆有用的可能性，如在一些自身免疫性疾病和一些病毒感染中。
Cytotoxic T lymphocytes (CTLs) have been shown to be relatively resistant to cytolytic attack by other CTLs. We show here, however, that cloned CTLs, in the absence of other cells, are destroyed by exposure to their cognate peptides (defined as those that in association with major histocompatibility complex proteins are recognized by the antigen-specific receptor of the T cell). Destruction is proportional to peptide concentration and can be prevented by a second peptide that competes with the cognate peptide for presentation by the class I major histocompatibility complex proteins of the CTLs. The speed and extent of peptide-induced changes in the appearance of CTLs suggest that the destruction may be due primarily to self-recognition and self-destruction of individual CTLs (suicide) rather than to the destruction of some CTLs by others of the same clone in the same culture (fratricide). This effect may also take place in vivo because the appropriately timed injection of a cognate peptide into ovalbumin-immunized mice appeared to deplete their spleens of primed anti-ovalbumin CTLs. The results point to a possible physiologic mechanism for postthymic elimination of cytolytic T cells that recognize their own peptides in association with their own major histocompatibility complex protein. The results also raise the possibility that cognate peptides might eventually prove therapeutically useful for eliminating CTL clones that cause pathological cell destruction, as in some autoimmune diseases and some viral infections.