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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Distinct influences of peptide-MHC quality and quantity on in vivo T-cell responses
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Distinct influences of peptide-MHC quality and quantity on in vivo T-cell responses

机译：肽MHC质量和数量对体内T细胞反应的不同影响

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摘要

The strength of T-cell receptor (TCR) stimulation and subsequent T-cell response depend on a combination of peptide-major histo-compatibility complex (pMHC) density and potency. By comparing two different pMHC at doses yielding similar proliferation in vivo, we have highlighted unexpected differences in the qualitative and quantitative effects of TCR ligand. Measurements of cytokine sensitivity and two-photon imaging of T cell-dendritic cell (T-DC) interactions reveal discrimination between comparably weak stimuli resulting from either decreased pMHC potency or pMHC density. In addition, TCR-induced genes in broad gene expression profiles segregate into two groups: one that responds to cumulative TCR signal and another that responds to pMHC quality, independent of quantity. These observations suggest that models of TCR ligand discrimination must account for disparate sensitivity of downstream responses to specific influences of pMHC potency.
机译：T细胞受体（TCR）刺激的强度和随后的T细胞反应取决于肽-主要组织相容性复合体（pMHC）密度和效能的组合。通过比较两种不同的pMHC剂量在体内产生相似的增殖，我们强调了TCR配体在定性和定量作用方面的出乎意料的差异。测量的细胞因子敏感性和T细胞-树突状细胞（T-DC）相互作用的双光子成像揭示了由降低的pMHC效力或pMHC密度导致的相对较弱的刺激之间的区别。此外，在广泛的基因表达谱中，TCR诱导的基因分为两组：一组响应累积的TCR信号，另一组响应pMHC质量，而与数量无关。这些观察结果表明，TCR配体识别模型必须考虑到下游反应对pMHC效能的特定影响的不同敏感性。

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  • 作者

    Rachel A. Gottschalk; Matthew M. Hathorn; Helene Beuneu; Emily Corse; Michael L. Dustin; Gregoire Altan-Bonnet; James P. Allison;

  • 作者单位

    Department of Immunology, Howard Hughes Medical Institute, and Ludwig Center for Cancer Immunotherapy, Memorial Sloan-Kettering Cancer Center,New York, NY 10065,Immunology and Microbial Pathogenesis Program, Weill Cornell Graduate School of Medical Sciences, New York, NY 10021;

    Immunology and Microbial Pathogenesis Program, Weill Cornell Graduate School of Medical Sciences, New York, NY 10021,Programs in Computational Biology and Immunology, Memorial Sloan-Kettering Cancer Center, New York, NY 10065;

    Program in Molecular Pathogenesis,Helen L. and Martin S. Kimmel Center for Biology and Medicine of the Skirball Institute of Biomolecular Medicine, New York University School of Medicine,New York, NY 10016;

    Department of Immunology, Howard Hughes Medical Institute, and Ludwig Center for Cancer Immunotherapy, Memorial Sloan-Kettering Cancer Center,New York, NY 10065;

    Program in Molecular Pathogenesis,Helen L. and Martin S. Kimmel Center for Biology and Medicine of the Skirball Institute of Biomolecular Medicine, New York University School of Medicine,New York, NY 10016;

    Programs in Computational Biology and Immunology, Memorial Sloan-Kettering Cancer Center, New York, NY 10065;

    Department of Immunology, Howard Hughes Medical Institute, and Ludwig Center for Cancer Immunotherapy, Memorial Sloan-Kettering Cancer Center,New York, NY 10065;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    affinity; IL-2; STAT5;

    机译：亲和力IL-2;STAT5;

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