Efficient cell activation requires an optimal dwell-time of interaction between the TCR and the pMHC complex
Efficient cell activation requires an optimal dwell-time of interaction between the TCR and the pMHC complex
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DOI：
10.1038/85286
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发表时间：
2001-03-01
影响因子：
30.5
通讯作者：
Nathenson, SG
中科院分区：
文献类型：
--
作者：
Kalergis, AM;Boucheron, N;Nathenson, SG
由抗原激活的细胞毒性T细胞(CTL)需要通过T细胞受体(TCR)对靶细胞表面的主要组织相容性I类(PMHC)分子进行特异性检测。我们检测了K-b限制性TCR抗原结合位点突变对T细胞活化、抗原结合和抗原解离的影响。使用这两个独立的系统，我们还检查了来自CTL克隆识别的K-d限制性多肽的变体的这些参数，我们表明，减少或增加TCR-pMHC相互作用的结合半衰期的突变可以削弱T细胞的激活。我们的数据表明，有效的T细胞激活发生在TCR-pMHC相互作用的最佳停留时间范围内。这一有限的停留时间范围与免疫反应期间将极低亲和力或高亲和力的T细胞排除在扩大的人群中是一致的。
Cytotoxic T cell (CTL) activation by antigen requires the specific detection of peptide-major histocompatibility class I (pMHC) molecules on the target-cell surface by the T cell receptor (TCR). We examined the effect of mutations in the antigen-binding site of a K-b-restricted TCR on T cell activation, antigen binding and dissociation from antigen. These parameters were also examined for variants derived from a K-d-restricted peptide that was recognized by a CTL clone, Using these two independent systems, we show that T cell activation can be impaired by mutations that either decrease or increase the binding half-life of the TCR-pMHC interaction. Our data indicate that efficient T cell activation occurs within an optimal dwell-time range of TCR-pMHC interaction. This restricted dwell-time range is consistent with the exclusion of either extremely low or high affinity T cells from the expanded population during immune responses.