Peptide-independent recognition by alloreactive cytotoxic T lymphocytes (CTL).
Peptide-independent recognition by alloreactive cytotoxic T lymphocytes (CTL).
复制标题
同种异体反应性细胞毒性 T 淋巴细胞 (CTL) 进行不依赖于肽的识别。
DOI：
10.1084/jem.185.6.1023
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发表时间：
1997
期刊：
影响因子：
--
通讯作者：
Potter,TA
中科院分区：
文献类型：
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作者：
Smith,PA;Brunmark,A;Jackson,MR;Potter,TA
我们已经分离出几种H-2Kb同种异体反应性细胞毒性T细胞克隆，并分析了它们对几种形式的H-2Kb的反应性。这些细胞毒性T淋巴细胞（CTL）引发与皮肤移植物，然后在体外刺激，使用刺激细胞表达的H-2Kb分子不能结合CD 8。与大多数同种异体反应性T细胞相反，这些CTL能够识别抗原加工缺陷细胞系RMA-S和T2表面上的H-2Kb。此外，通过添加含有来自C57 BL/6（H-2b）脾细胞的肽的提取物，该反应性没有增加，通过用酸处理靶细胞以去除与MHC分子结合的肽，该反应性也没有降低。CTL也能够识别表达突变H-2Kbm 8分子的靶标。这些结果表明，克隆识别的决定簇的H-2Kb是独立的肽。该假设的进一步证据由实验提供，在该实验中，在黑腹果蝇细胞中产生并固定在组织培养板表面上的H-2Kb能够刺激源自这些同种异体反应性T细胞的杂交瘤。前体频率分析表明，皮肤移植物引发，无论是与皮肤表达野生型或突变体H-2Kb分子，是一个强刺激，引发肽非依赖性CTL。此外，重建实验表明，非肽依赖性CTL克隆能够介导H-2不相容皮肤移植物的快速和完全排斥反应。这些发现提供了证据，证明并非所有同种识别都是肽依赖性的。
We have isolated several H-2Kb–alloreactive cytotoxic T cell clones and analyzed their reactivity for several forms of H-2Kb. These cytotoxic T lymphocytes (CTL) were elicited by priming with a skin graft followed by in vitro stimulation using stimulator cells that express an H-2Kb molecule unable to bind CD8. In contrast to most alloreactive T cells, these CTL were able to recognize H-2Kb on the surface of the antigen processing defective cell lines RMA-S and T2. Furthermore, this reactivity was not increased by the addition of an extract containing peptides from C57BL/6 (H-2b) spleen cells, nor was the reactivity decreased by treating the target cells with acid to remove peptides bound to MHC molecules. The CTL were also capable of recognizing targets expressing the mutant H-2Kbm8 molecule. These findings suggested that the clones recognized determinants on H-2Kb that were independent of peptide. Further evidence for this hypothesis was provided by experiments in which H-2Kb produced in Drosophila melanogaster cells and immobilized on the surface of a tissue culture plate was able to stimulate hybridomas derived from these alloreactive T cells. Precursor frequency analysis demonstrated that skin graft priming, whether with skin expressing the wild-type or the mutant H-2Kb molecule, is a strong stimulus to elicit peptide-independent CTL. Moreover, reconstitution experiments demonstrated that the peptide-independent CTL clones were capable of mediating rapid and complete rejection of H-2–incompatible skin grafts. These findings provide evidence that not all allorecognition is peptide dependent.