Komatsu H, Sierro S, V Cuero A, Klenerman P
Nuffield Department of Medicine, Peter Medawar Building for Pathogen Research, Oxford, UK.
Clin Exp Immunol. 2003 Oct;134(1):9-12. doi: 10.1046/j.1365-2249.2003.02266.x.
MHC class I-peptide tetrameric complexes ('tetramers') have revolutionized the study of antiviral CD8+ T cell responses. They allow accurate quantification of immune responses ex vivo independent of function, with high levels of sensitivity. They have revealed unexpectedly large frequencies of 'memory' T cell responses against viruses such as cytomegalovirus (CMV) and Epstein-Barr virus (EBV), and provided information about their phenotypic and functional variation. However, such studies have generally concentrated on limited numbers of individuals analysed in detail. To allow larger population-based studies, we devised a method for tetramer analysis using 50-100 microlitre blood volumes in a 96-well plate format. We adapted this method to study the effect of age on responses in a cohort of nearly 600 individuals to an immunodominant HLA-A2 restricted response to CMV pp65 (NLVPMVATV). We observed the phenomenon of steady 'memory inflation' with age, similar to recently observed longitudinal data from murine studies. These data show that tetramers can be used as population screening tools and could be used to study age-related, geographical or seasonal effects in a number of other viral infections.
主要组织相容性复合体I类-肽四聚体复合物（“四聚体”）彻底改变了抗病毒CD8 + T细胞反应的研究。它们能够在体外独立于功能精确量化免疫反应，具有高度的敏感性。它们揭示了针对巨细胞病毒（CMV）和爱泼斯坦-巴尔病毒（EBV）等病毒的“记忆”T细胞反应频率出人意料地高，并提供了有关其表型和功能变异的信息。然而，此类研究通常集中在对有限数量的个体进行详细分析。为了开展更大规模的基于人群的研究，我们设计了一种在96孔板中使用50 - 100微升血样进行四聚体分析的方法。我们采用这种方法研究了近600名个体组成的队列中年龄对针对CMV pp65（NLVPMVATV）的免疫显性HLA - A2限制性反应的影响。我们观察到随着年龄增长出现稳定的“记忆膨胀”现象，类似于最近从小鼠研究中观察到的纵向数据。这些数据表明，四聚体可用作人群筛查工具，并可用于研究许多其他病毒感染中与年龄、地理或季节相关的影响。
