Tanaka Y, Sano S, Nieves E, De Libero G, Rosa D, Modlin R L, Brenner M B, Bloom B R, Morita C T
Howard Hughes Medical Institute, Albert Einstein College of Medicine, Bronx, NY 10461.
Proc Natl Acad Sci U S A. 1994 Aug 16;91(17):8175-9. doi: 10.1073/pnas.91.17.8175.
gamma delta T cells respond to a variety of microbial pathogens and transformed cells. Their limited receptor repertoire and activation by mycobacterial antigens resistant to proteases suggest that they may recognize nonpeptide antigens. We have tested a variety of nonpeptide molecules for stimulation of human gamma delta T cells. Synthetic alkyl phosphates, particularly monoethyl phosphate (MEP), selectively activated gamma delta T cells and stimulated their proliferation in vitro. All gamma delta T cells stimulated by MEP expressed V gamma 2/V delta 2 receptors. The purified natural ligand of mycobacteria is chemically similar to, though distinct from, MEP and contains a phosphate residue that is critical for biological activity. Recognition and expansion of a specific T-cell receptor-bearing population to non-peptide ligands is unprecedented among T cells. We suggest that MEP mimics small natural ligands capable of expanding one subset of gamma delta T cells and that this recognition of nonpeptide antigens may play an important role in human immunity to pathogens.
γδ T细胞对多种微生物病原体和转化细胞有反应。它们有限的受体库以及对蛋白酶抗性的分枝杆菌抗原的激活表明它们可能识别非肽抗原。我们已经测试了多种非肽分子对人γδ T细胞的刺激作用。合成烷基磷酸盐，特别是单乙基磷酸盐（MEP），能选择性地激活γδ T细胞并在体外刺激它们增殖。所有被MEP刺激的γδ T细胞都表达Vγ2/Vδ2受体。分枝杆菌的纯化天然配体在化学上与MEP相似但又不同，并且含有对生物活性至关重要的磷酸残基。在T细胞中，识别并扩增携带特定T细胞受体的群体以响应非肽配体是前所未有的。我们认为MEP模拟了能够扩增γδ T细胞一个亚群的小天然配体，并且这种对非肽抗原的识别可能在人类对病原体的免疫中起重要作用。
