Amino acid similarity accounts for T cell cross-reactivity and for "holes" in the T cell repertoire.
Amino acid similarity accounts for T cell cross-reactivity and for "holes" in the T cell repertoire.
复制标题
氨基酸相似性说明T细胞交叉反应性和T细胞库中的“孔”。
DOI：
10.1371/journal.pone.0001831
复制
发表时间：
2008-03-19
期刊：
影响因子：
3.7
通讯作者：
Kesmir, Can
中科院分区：
文献类型：
--
作者：
Frankild, Sune;de Boer, Rob J.;Lund, Ole;Nielsen, Morten;Kesmir, Can
细胞毒性T细胞（CTL）交叉反应性被认为在产生免疫应答中起关键作用，但CTL交叉反应性的程度和机制仍不清楚。一些研究表明，CTL克隆可以识别高度多样化的肽，有些没有明显的序列同一性。该领域的新兴认识是T细胞受体（TcR）识别多种不同的配体。首先，我们分析了HIV表位SLFNTVATL （SFL9）的肽扫描，发现TCR特异性依赖于位置，生化相似的氨基酸替换不会显著影响识别。受此启发，我们开发了一个使用氨基酸相似矩阵的TCR肽识别通用模型，并发现该模型能够预测多种CTL表位的交叉反应性。有了这个模型，我们能够证明，表面上不同的T细胞表位，即具有低序列同一性的表位，实际上比预期的更生化相似。此外，用我们的模型对HIV免疫原性数据进行的分析表明，ctl倾向于主要对不类似于自身抗原的肽作出反应。因此，在某种程度上，T细胞的交叉反应性可以用氨基酸相似性来解释。本文提出的结果将有助于解决在T细胞交叉反应性领域的一些长期讨论。
Cytotoxic T cell (CTL) cross-reactivity is believed to play a pivotal role in generating immune responses but the extent and mechanisms of CTL cross-reactivity remain largely unknown. Several studies suggest that CTL clones can recognize highly diverse peptides, some sharing no obvious sequence identity. The emerging realization in the field is that T cell receptors (TcR) recognize multiple distinct ligands. First, we analyzed peptide scans of the HIV epitope SLFNTVATL (SFL9) and found that TCR specificity is position dependent and that biochemically similar amino acid substitutions do not drastically affect recognition. Inspired by this, we developed a general model of TCR peptide recognition using amino acid similarity matrices and found that such a model was able to predict the cross-reactivity of a diverse set of CTL epitopes. With this model, we were able to demonstrate that seemingly distinct T cell epitopes, i.e., ones with low sequence identity, are in fact more biochemically similar than expected. Additionally, an analysis of HIV immunogenicity data with our model showed that CTLs have the tendency to respond mostly to peptides that do not resemble self-antigens. T cell cross-reactivity can thus, to an extent greater than earlier appreciated, be explained by amino acid similarity. The results presented in this paper will help resolving some of the long-lasting discussions in the field of T cell cross-reactivity.
登录
查看更多内容
影响因子：
5.4
作者：
Larsen, MV;Lundegaard, C;Nielsen, M
通讯作者：
Nielsen, M
影响因子：
5.4
作者：
Höhn, H;Kortsik, C;Maeurer, MJ
通讯作者：
Maeurer, MJ
肽与MHC-I分子结合的社区资源基准预测。
影响因子：
4.3
作者：
Peters, Bjoern;Bui, Huynh-Hoa;Frankild, Sune;Nielsen, Morten;Lundegaard, Claus;Kostem, Emrah;Basch, Derek;Lamberth, Kasper;Harndahl, Mikkel;Fleri, Ward;Wilson, Stephen S.;Sidney, John;Lund, Ole;Buus, Soren;Sette, Alessandro
通讯作者：
Sette, Alessandro
影响因子：
30.5
作者：
Brehm, MA;Pinto, AK;Selin, LK
通讯作者：
Selin, LK
影响因子：
3.7
作者：
Rolland, Morgane;Nickle, David C.;Mullins, James I.
通讯作者：
Mullins, James I.