T cell affinity maturation by selective expansion during infection.
T cell affinity maturation by selective expansion during infection.
复制标题
T细胞亲和力通过在感染过程中选择性扩张而成熟。
DOI：
10.1084/jem.189.4.701
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发表时间：
1999-02-15
影响因子：
15.3
通讯作者：
Pamer, E G
中科院分区：
文献类型：
--
作者：
Busch, D H;Pamer, E G
T 淋巴细胞对受感染细胞的识别是由 T 细胞受体 (TCR) 与其配体、与病原体衍生肽复合的自身主要组织相容性复合物 (MHC) 分子相互作用介导的。 TCR 与受感染细胞上潜在少量 MHC/肽复合物的连续相互作用传递信号，导致 T 淋巴细胞扩增和效应功能激活。 TCR 对 MHC/肽复合物的亲和力对体内 T 细胞扩增的速率或程度的影响尚不清楚。在这里，我们表明，细菌感染后复杂 T 细胞群的体内扩增伴随着它们对抗原的总体亲和力的增加。经过额外几轮体内扩增的 T 细胞群表达的 TCR 范围更窄，在细胞毒性 T 淋巴细胞测定中对抗原的敏感性增加，并以更大的亲和力结合 MHC/肽复合物。高亲和力 T 细胞的选择性扩增提供了优化受感染细胞早期检测的体内机制。
T lymphocyte recognition of infected cells is mediated by T cell receptors (TCRs) interacting with their ligands, self–major histocompatibility complex (MHC) molecules complexed with pathogen-derived peptides. Serial TCR interactions with potentially small numbers of MHC/ peptide complexes on infected cells transmit signals that result in T lymphocyte expansion and activation of effector functions. The impact of TCR affinity for MHC/peptide complexes on the rate or extent of in vivo T cell expansion is not known. Here we show that in vivo expansion of complex T cell populations after bacterial infection is accompanied by an increase in their overall affinity for antigen. T cell populations that have undergone additional rounds of in vivo expansion express a narrower range of TCRs, have increased sensitivity for antigen in cytotoxic T lymphocyte assays, and bind MHC/peptide complexes with greater affinity. The selective expansion of higher affinity T cells provides an in vivo mechanism for optimizing the early detection of infected cells.