The inability to process a self-peptide allows autoreactive T cells to escape tolerance.
The inability to process a self-peptide allows autoreactive T cells to escape tolerance.
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DOI：
10.1084/jem.177.2.567
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发表时间：
1993-02-01
期刊：
影响因子：
--
通讯作者：
Mamula MJ
中科院分区：
文献类型：
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作者：
Mamula MJ
现在清楚的是，抗原呈递细胞（APC）并不将自身蛋白的所有可能的肽呈递给免疫系统。到那时，T细胞的命运是否对那些逃避处理的自身肽具有特异性？在这项研究中，自身细胞色素c（cyt c）的COOH-末端肽（残基81-104）引起强烈的自身免疫性T细胞，以及对这种免疫原特异性的自身抗体。这些T细胞对整个自身cyt c分子的刺激没有反应，表明APC不能加工和呈递自身81-104肽。尽管小鼠对用完整的小鼠cyt c分子免疫无应答，但小鼠81-104片段与完整的自身分子一起诱导并扩增了对1-80肽内位点的自身免疫T细胞应答。从不接触相关自身肽的T细胞是功能无知的。它们不会被耐受化或缺失，也不会正常参与对天然完整自身蛋白的免疫应答，因为APC不能呈递81-104肽。
It is now clear that antigen presenting cells (APCs) do not present all the possible peptides of self-proteins to the immune system. When then, is the fate of T cells specific for those self-peptides that escape processing? In this study, the COOH-terminal peptide (residues 81-104) of self cytochrome c (cyt c) elicited strong autoimmune T cells, as well as autoantibodies specific for this immunogen. These T cells did not respond to stimulation with the whole self cyt c molecule, demonstrating that APCs cannot process and present the self 81-104 peptide. Whereas mice were unresponsive to immunization with the whole mouse cyt c molecule, the mouse 81-104 fragment together with the whole self-molecule induced and amplified the autoimmune T cell response to sites within the 1-80 peptide. T cells that never contact the relevant self-peptide are functionally ignorant. They do not become tolerized or deleted, nor do they normally participate in immune responses to the native whole self-protein, since APCs cannot present the 81-104 peptide.