Levitsky V, de Campos-Lima P O, Frisan T, Masucci M G
Microbiology and Tumorbiology Center, Karolinska Institute, Stockholm, Sweden.
J Immunol. 1998 Jul 15;161(2):594-601.
The TCR repertoire of a peptide-specific HLA A11-restricted CTL response to persistent infection with EBV was followed for a period of 57 mo. Sequencing of TCR V alpha and V beta chains and alanine scanning mutagenesis analysis of 83 CTL clones isolated in five reactivation experiments demonstrated that this repertoire is composed of at least four distinct CTL clonotypes that are constantly reactivated from donor's blood and express structurally heterogeneous TCRs. Target cell recognition and CD8 blocking experiments indicate that the four clonotypes possess different avidity and TCR affinity for the specific Ag. This demonstrates that at least in some individuals a heterogeneous peptide-specific memory CTL repertoire selected by a persistent Ag can be remarkably stable in time and accommodate a range of TCR affinities and T cell avidities. Our results suggest that competition for the specific Ag may be not the major force driving the maintenance of memory CTLs and that the nature of the first antigenic challenge may largely determine the clonal composition of memory.
对EB病毒持续感染产生的肽特异性HLA A11限制性CTL反应的TCR库进行了57个月的跟踪研究。对在五次再激活实验中分离出的83个CTL克隆进行TCR Vα和Vβ链测序以及丙氨酸扫描诱变分析，结果表明该TCR库至少由四种不同的CTL克隆型组成，这些克隆型不断从供体血液中再激活，并表达结构异质的TCR。靶细胞识别和CD8阻断实验表明，这四种克隆型对特异性抗原具有不同的亲和力和TCR亲和力。这表明，至少在某些个体中，由持续抗原选择的异质肽特异性记忆CTL库在时间上可以非常稳定，并能容纳一系列TCR亲和力和T细胞亲和力。我们的结果表明，对特异性抗原的竞争可能不是驱动记忆CTL维持的主要力量，并且首次抗原刺激的性质可能在很大程度上决定记忆的克隆组成。
