Broadly targeted CD8+ T cell responses restricted by major histocompatibility complex E

被引：236

作者：

Hansen, Scott G. ^{[1
,2
]}

Wu, Helen L. ^{[1
,2
]}

Burwitz, Benjamin J. ^{[1
,2
]}

Hughes, Colette M. ^{[1
,2
]}

Hammond, Katherine B. ^{[1
,2
]}

Ventura, Abigail B. ^{[1
,2
]}

Reed, Jason S. ^{[1
,2
]}

Gilbride, Roxanne M. ^{[1
,2
]}

Ainslie, Emily ^{[1
,2
]}

Morrow, David W. ^{[1
,2
]}

Ford, Julia C. ^{[1
,2
]}

Selseth, Andrea N. ^{[1
,2
]}

Pathak, Reesab ^{[1
,2
]}

Malouli, Daniel ^{[1
,2
]}

Legasse, Alfred W. ^{[1
,2
]}

Axthelm, Michael K. ^{[1
,2
]}

Nelson, Jay A. ^{[1
,2
]}

Gillespie, Geraldine M. ^{[3
]}

Walters, Lucy C. ^{[3
]}

Brackenridge, Simon ^{[3
]}

Sharpe, Hannah R. ^{[3
]}

Lopez, Cesar A. ^{[4
]}

Frueh, Klaus ^{[1
,2
]}

Korber, Bette T. ^{[4
,5
]}

McMichael, Andrew J. ^{[3
]}

Gnanakaran, S. ^{[4
]}

Sacha, Jonah B. ^{[1
,2
]}

Picker, Louis J. ^{[1
,2
]}

机构：

[1] Oregon Hlth & Sci Univ, Vaccine & Gene Therapy Inst, Beaverton, OR 97006 USA

[2] Oregon Hlth & Sci Univ, Oregon Natl Primate Res Ctr, Beaverton, OR 97006 USA

[3] Univ Oxford, Nuffield Dept Med, Oxford OX37FZ, England

[4] Los Alamos Natl Lab, Theoret Biol & Biophys Grp, POB 1663, Los Alamos, NM 87545 USA

[5] New Mexico Consortium, Los Alamos, NM 87545 USA

来源：

SCIENCE | 2016年 / 351卷 / 6274期

关键词：

MHC-CLASS-I; HIGHLY PATHOGENIC SIV; HLA-E EXPRESSION; SURFACE EXPRESSION; RECEPTORS; BINDING; RHESUS;

D O I：

10.1126/science.aac9475

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Major histocompatibility complex E (MHC-E) is a highly conserved, ubiquitously expressed, nonclassical MHC class Ib molecule with limited polymorphism that is primarily involved in the regulation of natural killer (NK) cells. We found that vaccinating rhesus macaques with rhesus cytomegalovirus vectors in which genes Rh157.5 and Rh157.4 are deleted results in MHC-E-restricted presentation of highly varied peptide epitopes to CD8 alpha beta(+) T cells, at similar to 4 distinct epitopes per 100 amino acids in all tested antigens. Computational structural analysis revealed that MHC-E provides heterogeneous chemical environments for diverse side-chain interactions within a stable, open binding groove. Because MHC-E is up-regulated to evade NK cell activity in cells infected with HIV, simian immunodeficiency virus, and other persistent viruses, MHC-E-restricted CD8(+) T cell responses have the potential to exploit pathogen immune-evasion adaptations, a capability that might endow these unconventional responses with superior efficacy.

引用

页码：714 / 720

页数：9

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