Sylwester Andrew, Nambiar Kate Z, Caserta Stefano, Klenerman Paul, Picker Louis J, Kern Florian
Vaccine & Gene Therapy Institute, Oregon Health & Science University West Campus, Beaverton, OR 97006, USA.
Division of Medicine, Brighton and Sussex Medical School, Brighton BN1 9PX, United Kingdom.
Mech Ageing Dev. 2016 Sep;158:14-22. doi: 10.1016/j.mad.2016.03.002. Epub 2016 Mar 5.
In studies exploring the effects of HCMV infection on immune system aging ('immunosenescence'), after organ transplantation or in other settings, HCMV-specific T-cell responses are often assessed with respect to purportedly 'immunodominant' protein subunits. However, the response structure in terms of recognized antigens and response hierarchies (architecture) is not well understood and actual correlates of immune protection are not known.
We explored the distribution of T-cell response sizes and dominance hierarchies as well as response breadth in 33 HCMV responders with respect to >200 HCMV proteins.
At the individual responder level HCMV-specific T-cell responses were generally arranged in clear dominance hierarchies; interestingly, the number of proteins recognized by an individual correlated closely with the size of their biggest response. Target-specificity varied considerably between donors and across hierarchy levels with the presence, size, and hierarchy position of responses to purportedly 'immunodominant' targets being unpredictable.
Predicting protective immunity based on isolated HCMV subunit-specific T-cell responses is questionable in light of the complex architecture of the overall response. Our findings have important implications for T-cell monitoring, intervention strategies, as well as the application of animal models to the understanding of human infection.
在探索人巨细胞病毒（HCMV）感染对免疫系统衰老（“免疫衰老”）的影响、器官移植后或其他情况下的研究中，HCMV特异性T细胞反应通常针对所谓的“免疫显性”蛋白亚基进行评估。然而，关于识别抗原和反应层次结构（架构）方面的反应结构尚未得到充分理解，免疫保护的实际相关因素也不清楚。
我们针对超过200种HCMV蛋白，探究了33名HCMV反应者中T细胞反应大小的分布、优势层次以及反应广度。
在个体反应者水平上，HCMV特异性T细胞反应通常以明确的优势层次排列；有趣的是，个体识别的蛋白数量与其最大反应的大小密切相关。供体之间以及不同层次水平之间的靶点特异性差异很大，对所谓“免疫显性”靶点的反应的存在、大小和层次位置都无法预测。
鉴于总体反应的复杂架构，基于分离的HCMV亚基特异性T细胞反应来预测保护性免疫是值得怀疑的。我们的发现对T细胞监测、干预策略以及动物模型在理解人类感染中的应用具有重要意义。
