Epitope-dependent selection of highly restricted or diverse T cell receptor repertoires in response to persistent infection by Epstein-Barr virus.
Epitope-dependent selection of highly restricted or diverse T cell receptor repertoires in response to persistent infection by Epstein-Barr virus.
复制标题
高度受限或多样化的 T 细胞受体库的表位依赖性选择，以响应 Epstein-Barr 病毒的持续感染。
DOI：
10.1084/jem.186.1.83
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发表时间：
1997-07-07
影响因子：
15.3
通讯作者：
Masucci, M G
中科院分区：
文献类型：
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作者：
Campos-Lima, P O;Levitsky, V;Imreh, M P;Gavioli, R;Masucci, M G
研究了4名健康EB病毒携带者对EB病毒核抗原4中免疫显性和亚显性HLAA 11限制性表位的T细胞受体（TCR）的细胞毒性反应。对亚显性表位（EBNA 4 399-408，命名为AVF）的应答高度受限于保守的Vβ使用以及第三互补决定区（CDR 3）中相同的长度和氨基酸基序，而免疫显性表位（EBNA 4 416-424，命名为IVT）选择了使用TCR-α/β V和J区段与CDR 3区的不同组合的广泛库。通过丙氨酸扫描诱变分析，揭示了每个AVF或IVT特异性TCR克隆型与A11-肽复合物相互作用的独特模式。通过对CD 8辅助受体特异性的抗体阻断细胞毒性功能表明，虽然AVF特异性TCR具有高亲和力，但对IVT表位的寡克隆应答包括低亲和力和高亲和力TCR。因此，对来自相同病毒抗原并通过相同MHC I类等位基因呈递的两个表位的记忆应答的比较表明，免疫显性可能与维持广泛TCR库的能力相关。
The T cell receptor (TCR) repertoires of cytotoxic responses to the immunodominant and subdominant HLA A11–restricted epitopes in the Epstein-Barr virus (EBV) nuclear antigen-4 were investigated in four healthy virus carriers. The response to the subdominant epitope (EBNA4 399-408, designated AVF) was highly restricted with conserved Vβ usage and identical length and amino acid motifs in the third complementarity-determining regions (CDR3), while a broad repertoire using different combinations of TCR-α/β V and J segments and CDR3 regions was selected by the immunodominant epitope (EBNA4 416-424, designated IVT). Distinct patterns of interaction with the A11–peptide complex were revealed for each AVF- or IVT-specific TCR clonotype by alanine scanning mutagenesis analysis. Blocking of cytotoxic function by antibodies specific for the CD8 coreceptor indicated that, while AVF-specific TCRs are of high affinity, the oligoclonal response to the IVT epitope includes both low- and high-affinity TCRs. Thus, comparison of the memory response to two epitopes derived from the same viral antigen and presented through the same MHC class I allele suggests that immunodominance may correlate with the capacity to maintain a broad TCR repertoire.