Rapid T Cell Receptor Delineation Reveals Clonal Expansion Limitation of the Magnitude of the HIV-1-Specific CD8+ T Cell Response
Rapid T Cell Receptor Delineation Reveals Clonal Expansion Limitation of the Magnitude of the HIV-1-Specific CD8+ T Cell Response
复制标题
DOI：
10.4049/jimmunol.1002236
复制
发表时间：
2010-11-15
影响因子：
4.4
通讯作者：
Yang, Otto O.
中科院分区：
文献类型：
--
作者：
Balamurugan, Arumugam;Ng, Hwee L.;Yang, Otto O.
TCR介导CTL特异性，但识别相同表位的TCR由于其随机衍生而在人与人之间经常不同。这种变异性在病毒感染和恶性肿瘤发病机制中的作用在技术上很难研究。我们应用TCR谱分析的适应性来研究HIV特异性CTL，定义来自PBMC的表位特异性TCR的克隆宽度和序列，而无需细胞分选或分子克隆。检查12人的48个CTL应答，揭示了公共和私人克隆型的每个应答平均4.5 +/-2.7个克隆。鉴定的表位特异性TCR的数量与跨表位的CTL频率相关，表明克隆宽度限制了体内针对HIV-1的CTL应答的幅度。在这个小的队列中，HLA A和B限制性CTL的TCR宽度相似，初步表明定性差异可能是它们对发病机制的不同影响的原因。总体而言，这些发现表明，慢性HIV-1感染中的CTL应答的幅度受到TCR克隆宽度的限制，表明CTL应答慢性抗原刺激的最大扩增。免疫学杂志，2010，185：5935-5942。
TCRs mediate CTL specificity, but TCRs recognizing the same epitope often differ between persons due to their stochastic derivation. The role of this variability in the pathogenesis of virus infections and malignancies has been technically difficult to study. We apply an adaptation of TCR spectratyping to study HIV-specific CTLs, defining the clonal breadth and sequences of epitopespecific TCRs from PBMCs without cellular sorting or molecular cloning. Examining 48 CTL responses in 12 persons reveals a mean of 4.5 +/- 2.7 clones per response, of both public and private clonotypes. The number of identified epitope-specific TCRs correlates with CTL frequency across epitopes, suggesting that clonal breadth limits the magnitude of the CTL response against HIV-1 in vivo. HLA A- and B-restricted CTLs are similar in their TCR breadth in this small cohort, preliminarily suggesting that qualitative differences may account for their disparate impacts on pathogenesis. Overall, these findings demonstrate that the magnitude of the CTL response in chronic HIV-1 infection is constrained by TCR clonal breadth, suggesting maximal expansion of CTLs in response to chronic antigenic stimulation. The Journal of Immunology, 2010, 185: 5935-5942.