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DOI | 10.1126/science.aav5095 |
VACCINOLOGY Structural topology defines protective CD8(+) T cell epitopes in the HIV proteome | |
Gaiha, Gaurav D.1,2; Rossin, Elizabeth J.3,4; Urbach, Jonathan1; Landeros, Christian1; Collins, David R.1,5; Nwonu, Chioma1; Muzhingi, Itai1; Anahtar, Melis N.1,6; Waring, Olivia M.1,7; Piechocka-Trocha, Alicja1,5; Waring, Michael1,5; Worrall, Daniel P.1; Ghebremichael, Musie S.1; Newman, Ruchi M.1; Power, Karen A.1; Allen, Todd M.1; Chodosh, James4; Walker, Bruce D.1,3,5,7 | |
2019-05-03 | |
发表期刊 | SCIENCE
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ISSN | 0036-8075 |
EISSN | 1095-9203 |
出版年 | 2019 |
卷号 | 364期号:6439页码:480-+ |
文章类型 | Article |
语种 | 英语 |
国家 | USA |
英文摘要 | Mutationally constrained epitopes of variable pathogens represent promising targets for vaccine design but are not reliably identified by sequence conservation. In this study, we employed structure-based network analysis, which applies network theory to HIV protein structure data to quantitate the topological importance of individual amino acid residues. Mutation of residues at important network positions disproportionately impaired viral replication and occurred with high frequency in epitopes presented by protective human leukocyte antigen (HLA) class I alleles. Moreover, CD8(+) T cell targeting of highly networked epitopes distinguished individuals who naturally control HIV, even in the absence of protective HLA alleles. This approach thereby provides a mechanistic basis for immune control and a means to identify CD8(+) T cell epitopes of topological importance for rational immunogen design, including a T cell-based HIV vaccine. |
领域 | 地球科学 ; 气候变化 ; 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000466809600033 |
WOS关键词 | MAJOR DETERMINANTS ; CONSERVATION ; RESPONSES ; ESCAPE ; POINT ; MUTATIONS ; EVOLUTION ; SELECTION ; PROTEINS ; MUTANTS |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/201351 |
专题 | 地球科学 资源环境科学 气候变化 |
作者单位 | 1.Ragon Inst MGH MIT & Harvard, Cambridge, MA 02139 USA; 2.Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA; 3.Broad Inst MIT & Harvard, Cambridge, MA 02142 USA; 4.Massachusetts Eye & Ear, Dept Ophthalmol, Boston, MA 02114 USA; 5.Howard Hughes Med Inst, Chevy Chase, MD 20815 USA; 6.Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA; 7.MIT, Inst Med Engn & Sci, 77 Massachusetts Ave, Cambridge, MA 02139 USA |
推荐引用方式 GB/T 7714 | Gaiha, Gaurav D.,Rossin, Elizabeth J.,Urbach, Jonathan,et al. VACCINOLOGY Structural topology defines protective CD8(+) T cell epitopes in the HIV proteome[J]. SCIENCE,2019,364(6439):480-+. |
APA | Gaiha, Gaurav D..,Rossin, Elizabeth J..,Urbach, Jonathan.,Landeros, Christian.,Collins, David R..,...&Walker, Bruce D..(2019).VACCINOLOGY Structural topology defines protective CD8(+) T cell epitopes in the HIV proteome.SCIENCE,364(6439),480-+. |
MLA | Gaiha, Gaurav D.,et al."VACCINOLOGY Structural topology defines protective CD8(+) T cell epitopes in the HIV proteome".SCIENCE 364.6439(2019):480-+. |
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