High-throughput characterization of HLA-E-presented CD94/NKG2x ligands reveals peptides which modulate NK cell activation.
High-throughput characterization of HLA-E-presented CD94/NKG2x ligands reveals peptides which modulate NK cell activation.
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DOI：
10.1038/s41467-023-40220-1
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发表时间：
2023-08-09
影响因子：
16.6
通讯作者：
Birnbaum, Michael E. E.
中科院分区：
文献类型：
--
作者：
Huisman, Brooke D. D.;Guan, Ning;Rueckert, Timo;Garner, Lee;Singh, Nishant K. K.;McMichael, Andrew J. J.;Gillespie, Geraldine M. M.;Romagnani, Chiara;Birnbaum, Michael E. E.
HLA-E是一种非经典I类MHC蛋白，参与先天和适应性免疫识别。虽然最近的研究表明HLA-E可以向NK细胞和T细胞提供多种肽，但CD94/NKG2x识别的HLA-E库仍然定义不清，仅鉴定了有限数量的肽配体。在这里，我们筛选了酵母在HLA-E背景下显示的肽库，以鉴定500个高置信度的独特肽，这些肽可以结合HLA-E和CD94/NKG2A或CD94/NKG2C。利用酵母展示选择鉴定的序列，我们训练了预测算法，并鉴定了人类和巨细胞病毒（CMV）蛋白质组衍生的、hla - e呈递的肽，这些肽能够通过CD94/NKG2A和CD94/NKG2C结合和信号传导。此外，我们还鉴定了选择性激活NKG2C+ NK细胞的肽。总之，hla - e结合肽库的表征和NK活性调节肽的鉴定为研究NK细胞在健康和疾病中的调节，以及疫苗和治疗设计提供了机会。HLA-E是一种高度保守的mhc - 1，可被NK细胞和T细胞识别。作者描述了CD94/NKG2x识别的HLA-E呈递肽，鉴定了人类和cmv衍生的肽配体，这些配体可以在HLA-E呈递时调节NK细胞活性，包括选择性NK细胞活化。
HLA-E is a non-classical class I MHC protein involved in innate and adaptive immune recognition. While recent studies have shown HLA-E can present diverse peptides to NK cells and T cells, the HLA-E repertoire recognized by CD94/NKG2x has remained poorly defined, with only a limited number of peptide ligands identified. Here we screen a yeast-displayed peptide library in the context of HLA-E to identify 500 high-confidence unique peptides that bind both HLA-E and CD94/NKG2A or CD94/NKG2C. Utilizing the sequences identified via yeast display selections, we train prediction algorithms and identify human and cytomegalovirus (CMV) proteome-derived, HLA-E-presented peptides capable of binding and signaling through both CD94/NKG2A and CD94/NKG2C. In addition, we identify peptides which selectively activate NKG2C+ NK cells. Taken together, characterization of the HLA-E-binding peptide repertoire and identification of NK activity-modulating peptides present opportunities for studies of NK cell regulation in health and disease, in addition to vaccine and therapeutic design. HLA-E is a highly conserved MHC-l recognized by NK and T cells. The authors characterize HLA-E-presented peptides recognized by CD94/NKG2x, identifying human and CMV-derived peptide ligands which can modulate NK cell activity when presented by HLA-E, including for selective NK cell activation.
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NKG2A 与 CD94 复合定义了一种新型抑制性自然杀伤细胞受体。
DOI：
10.1084/jem.185.4.795
发表时间：
1997-02-17
期刊：
The Journal of experimental medicine
影响因子：
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作者：
Brooks AG;Posch PE;Scorzelli CJ;Borrego F;Coligan JE
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影响因子：
64.5
作者：
Gee MH;Han A;Lofgren SM;Beausang JF;Mendoza JL;Birnbaum ME;Bethune MT;Fischer S;Yang X;Gomez-Eerland R;Bingham DB;Sibener LV;Fernandes RA;Velasco A;Baltimore D;Schumacher TN;Khatri P;Quake SR;Davis MM;Garcia KC
通讯作者：
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影响因子：
64.5
作者：
Birnbaum ME;Mendoza JL;Sethi DK;Dong S;Glanville J;Dobbins J;Ozkan E;Davis MM;Wucherpfennig KW;Garcia KC
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Garcia KC
影响因子：
32.4
作者：
Abelin JG;Keskin DB;Sarkizova S;Hartigan CR;Zhang W;Sidney J;Stevens J;Lane W;Zhang GL;Eisenhaure TM;Clauser KR;Hacohen N;Rooney MS;Carr SA;Wu CJ
通讯作者：
Wu CJ
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