Negative selection and peptide chemistry determine the size of naive foreign peptide-MHC class II-specific CD4+ T cell populations.

Negative selection and peptide chemistry determine the size of naive foreign peptide-MHC class II-specific CD4+ T cell populations.
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DOI:
10.4049/jimmunol.1002276
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发表时间:
2010-10-15
期刊:
Journal of immunology (Baltimore, Md. : 1950)
影响因子:
--
通讯作者:
Jenkins MK
Jenkins MK
中科院分区:
其他
文献类型:
--
作者:
Chu HH;Moon JJ;Kruse AC;Pepper M;Jenkins MK

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表达对不同外源肽-MHCII(pMHCII)配体具有特异性的TCR的幼稚CD4 + T细胞群的大小可以在几个数量级上变化。这种变化可以解释为什么对某些肽的免疫反应比其他肽强。在这里,我们使用了一个敏感的pMHCII-四聚体为基础的细胞富集方法来研究两个幼稚的外来pMHCII特异性幼稚CD4 + T细胞群体的衍生,在正常小鼠中的大小相差8倍。对胸腺阴性选择受损的小鼠的分析显示,较小的群体比较大的群体经历更多的克隆缺失。此外,大的幼稚细胞群体倾向于识别具有色氨酸残基的肽作为TCR接触。因此,倾向于被大的初始群体识别的外源pMHCII诱导最小的克隆缺失,并且含有具有与TCR有利地相互作用的能力的某些氨基酸。
Naïve CD4+ T cell populations that express TCRs specific for different foreign peptide-MHCII (pMHCII) ligands can vary in size over several orders of magnitude. This variation may explain why immune responses to some peptides are stronger than others. Here we used a sensitive pMHCII-tetramer based cell enrichment method to study the derivation of two naïve foreign pMHCII-specific naïve CD4+ T cell populations that differed in size by 8-fold in normal mice. Analysis of mice in which thymic negative selection was impaired revealed that the smaller population underwent more clonal deletion than the larger population. In addition, large naïve cell populations tended to recognize peptides with tryptophan residues as TCR contacts. Thus, the foreign pMHCII that tend to be recognized by large naïve populations induce minimal clonal deletion and contain certain amino acids with the capacity to interact favorably with TCRs.
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