Peptide Binding to HLA-E Molecules in Humans, Nonhuman Primates, and Mice Reveals Unique Binding Peptides but Remarkably Conserved Anchor Residues.
Peptide Binding to HLA-E Molecules in Humans, Nonhuman Primates, and Mice Reveals Unique Binding Peptides but Remarkably Conserved Anchor Residues.
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人类、非人类灵长类动物和小鼠中与HLA-E分子结合的肽揭示了独特的结合肽，但显著保守的锚残基。
DOI：
10.4049/jimmunol.2000810
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发表时间：
2020-11-15
期刊：
影响因子：
--
通讯作者：
Joosten SA
中科院分区：
文献类型：
--
作者：
Ruibal P;Franken KLMC;van Meijgaarden KE;van Loon JJF;van der Steen D;Heemskerk MHM;Ottenhoff THM;Joosten SA
抗原通过非经典MHC类Ib分子HLA-E呈递，在人体内表达的两个等位基因HLA-E*01:01和HLA-E*01:03几乎完全相同，可导致人体内非常规t细胞的激活。尽管存在这种虚拟的遗传单态性，但已报道了与两种等位基因变体结合的肽库的差异。为了进一步分析和比较肽与HLA-E*01:01和HLA-E*01:03的结合，我们使用了紫外线介导的肽交换结合实验和基于高效液相色谱的竞争结合实验。此外，我们还研究了这些相同的肽与Mamu-E（人类HLA-E的非人类灵长类同源物）和小鼠HLA-E样分子Qa-1b的结合。接下来，我们利用这4个分子的肽结合口袋的差异和同源性来识别跨物种的等位基因特异性和肽结合基序的共同特征。我们的研究结果显示，与Mamu-E和Qa-1b相比，每个人HLA-E变体的肽结合偏好和强度存在差异。利用扩展的肽库，我们确定并细化了四个分子的肽结合基序，发现它们共享主锚位，在所研究的四个HLA-E分子中保守的氨基酸偏好证明了这一点。此外，我们还发现了肽结合基序的差异，这可以解释四种HLA-E样分子在肽结合偏好和亲和力方面的差异。我们的研究结果有助于指导候选病原体衍生肽的选择，这些肽具有靶向hla - e限制性t细胞的能力，可以在疫苗接种和免疫治疗策略中动员起来。
Antigen presentation via the non-classical MHC class Ib molecule HLA-E, with nearly complete identity between the two alleles expressed in humans, HLA-E*01:01 and HLA-E*01:03, can lead to the activation of unconventional T-cells in humans. Despite this virtual genetic monomorphism, differences in peptide repertoires binding to the two allelic variants have been reported. To further dissect and compare peptide binding to HLA-E*01:01 and HLA-E*01:03 we used a UV-mediated peptide exchange binding assay and an HPLC-based competition binding assay. In addition, we investigated binding of these same peptides to Mamu-E, the non-human primate homologue of human HLA-E, and to the HLA-E like molecule Qa-1b in mice. We next exploited the differences and homologies in the peptide binding pockets of these 4 molecules to identify allele-specific as well as common features of peptide binding motifs across species. Our results reveal differences in peptide binding preferences and intensities for each human HLA-E variant compared to Mamu-E and Qa-1b. Using extended peptide libraries, we identified and refined the peptide binding motifs for each of the four molecules and found that they share main anchor positions, evidenced by conserved amino acid preferences across the four HLA-E molecules studied. In addition, we also identified differences in peptide binding motifs which could explain the observed variations in peptide binding preferences and affinities for each of the four HLA-E like molecules. Our results could help guiding the selection of candidate pathogen-derived peptides with the capacity to target HLA-E-restricted T-cells that could be mobilized in vaccination and immunotherapeutic strategies.
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MTB衍生的抗原对人CD8+ T细胞的HLA-E依赖性表现。
影响因子：
15.3
作者：
Heinzel, Amy S;Grotzke, Jeff E;Lines, Rebecca A;Lewinsohn, Deborah A;McNabb, Andria L;Streblow, Daniel N;Braud, Veronique M;Grieser, Heather J;Belisle, John T;Lewinsohn, David M
通讯作者：
Lewinsohn, David M
DOI：
10.1126/science.aac9475
发表时间：
2016-02-12
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Hansen SG;Wu HL;Burwitz BJ;Hughes CM;Hammond KB;Ventura AB;Reed JS;Gilbride RM;Ainslie E;Morrow DW;Ford JC;Selseth AN;Pathak R;Malouli D;Legasse AW;Axthelm MK;Nelson JA;Gillespie GM;Walters LC;Brackenridge S;Sharpe HR;López CA;Früh K;Korber BT;McMichael AJ;Gnanakaran S;Sacha JB;Picker LJ
通讯作者：
Picker LJ
影响因子：
13.8
作者：
Combet, C;Blanchet, C;Deléage, G
通讯作者：
Deléage, G
影响因子：
3.7
作者：
Hansen, Scott G.;Womack, Jennie;Fruh, Klaus
通讯作者：
Fruh, Klaus
影响因子：
6.7
作者：
Joosten SA;van Meijgaarden KE;van Weeren PC;Kazi F;Geluk A;Savage ND;Drijfhout JW;Flower DR;Hanekom WA;Klein MR;Ottenhoff TH
通讯作者：
Ottenhoff TH