Naive CD4+ T cell frequency varies for different epitopes and predicts repertoire diversity and response magnitude

Naive CD4+ T cell frequency varies for different epitopes and predicts repertoire diversity and response magnitude
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DOI:
10.1016/j.immuni.2007.07.007
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发表时间:
2007-08-01
期刊:
影响因子:
32.4
通讯作者:
Jenkins, Marc K.
Jenkins, Marc K.
中科院分区:
医学1区
文献类型:
--
作者:
Moon, James J.;Chu, H. Hamlet;Jenkins, Marc K.

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细胞介导的免疫源于表达T细胞抗原受体(TCR)的初始T淋巴细胞的增殖,这些受体对与宿主主要组织相容性复合体(MHC)分子结合的外来肽具有特异性。由于T细胞库的巨大多样性,针对任何一种肽:MHC复合物(pMHC)的初始T细胞极为罕见。因此,尚不清楚体内存在多少具有任何给定pMHC特异性的初始T细胞,以及该数量如何影响免疫反应。通过使用可溶性II类pMHC(pMHCII)四聚体和磁珠富集,我们发现三种不同的pMHCII特异性初始CD4(+) T细胞群在每只小鼠中的频率从20到200个细胞不等。此外,初始群体大小预测了用相关肽免疫后初级CD4(+) T细胞反应的大小和TCR多样性。因此,初始T细胞频率的差异可以解释为什么某些肽比其他肽是更强的免疫原。
Cell-mediated immunity stems from the proliferation of naive T lymphocytes expressing T cell antigen receptors (TCRs) specific for foreign peptides bound to host major histocompatibility complex (MHC) molecules. Because of the tremendous diversity of the T cell repertoire, naive T cells specific for any one peptide:MHC complex (pMHC) are extremely rare. Thus, it is not known how many naive T cells of any given pMlHC specificity exist in the body or how that number influences the immune response. By using soluble pMHC class II (pMHCII) tetramers and magnetic bead enrichment, we found that three different pMHCII-specific naive CD4(+) T cell populations vary in frequency from 20 to 200 cells per mouse. Moreover, naive population size predicted the size and TCR diversity of the primary CD4(+) T cell response after immunization with relevant peptide. Thus, variation in naive T cell frequencies can explain why some peptides are stronger immunogens than others.