Neller Michelle A, Ladell Kristin, McLaren James E, Matthews Katherine K, Gostick Emma, Pentier Johanne M, Dolton Garry, Schauenburg Andrea J A, Koning Dan, Fontaine Costa Ana Isabel C A, Watkins Thomas S, Venturi Vanessa, Smith Corey, Khanna Rajiv, Miners Kelly, Clement Mathew, Wooldridge Linda, Cole David K, van Baarle Debbie, Sewell Andrew K, Burrows Scott R, Price David A, Miles John J
Human Immunity Laboratory, Cellular Immunology Laboratory and Tumour Immunology Laboratory, Queensland Institute of Medical Research, Brisbane, QLD, Australia.
Institute of Infection and Immunity, Cardiff University School of Medicine, Heath Park, Cardiff, UK.
Immunol Cell Biol. 2015 Aug;93(7):625-33. doi: 10.1038/icb.2015.17. Epub 2015 Mar 24.
Basic parameters of the naive antigen (Ag)-specific T-cell repertoire in humans remain poorly defined. Systematic characterization of this 'ground state' immunity in comparison with memory will allow a better understanding of clonal selection during immune challenge. Here, we used high-definition cell isolation from umbilical cord blood samples to establish the baseline frequency, phenotype and T-cell antigen receptor (TCR) repertoire of CD8(+) T-cell precursor populations specific for a range of viral and self-derived Ags. Across the board, these precursor populations were phenotypically naive and occurred with hierarchical frequencies clustered by Ag specificity. The corresponding patterns of TCR architecture were highly ordered and displayed partial overlap with adult memory, indicating biased structuring of the T-cell repertoire during Ag-driven selection. Collectively, these results provide new insights into the complex nature and dynamics of the naive T-cell compartment.
人类天然抗原（Ag）特异性T细胞库的基本参数仍未明确界定。与记忆性免疫相比，对这种“基础状态”免疫进行系统表征将有助于更好地理解免疫挑战期间的克隆选择。在此，我们从脐带血样本中进行高清细胞分离，以确定一系列病毒和自身来源抗原特异性CD8(+) T细胞前体群体的基线频率、表型和T细胞抗原受体（TCR）库。总体而言，这些前体群体在表型上呈天然状态，并以按抗原特异性聚类的分层频率出现。TCR结构的相应模式高度有序，且与成人记忆性免疫部分重叠，表明在抗原驱动的选择过程中T细胞库存在偏向性结构。这些结果共同为天然T细胞区室的复杂性质和动态提供了新的见解。
