Comprehensive analysis of dengue virus-specific responses supports an HLA-linked protective role for CD8+ T cells

被引：459

作者：

Weiskopf, Daniela ^{[1
]}

Angelo, Michael A. ^{[1
]}

de Azeredo, Elzinandes L. ^{[1
]}

Sidney, John ^{[1
]}

Greenbaum, Jason A. ^{[1
]}

Fernando, Anira N. ^{[2
]}

Broadwater, Anne ^{[3
]}

Kolla, Ravi V. ^{[1
]}

De Silva, Aruna D. ^{[1
,2
]}

de Silva, Aravinda M. ^{[3
]}

Mattia, Kimberly A. ^{[4
]}

Doranz, Benjamin J. ^{[4
]}

Grey, Howard M. ^{[1
]}

Shresta, Sujan ^{[1
]}

Peters, Bjoern ^{[1
]}

Sette, Alessandro ^{[1
]}

机构：

[1] La Jolla Inst Allergy & Immunol, Div Vaccine Discovery, La Jolla, CA 92037 USA

[2] Genetech Res Inst, Colombo 00800, Sri Lanka

[3] Univ N Carolina, Sch Med, Dept Microbiol & Immunol, Chapel Hill, NC 27599 USA

[4] Integral Mol, Philadelphia, PA 19104 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2013年 / 110卷 / 22期

基金：

美国国家卫生研究院;

关键词：

ORIGINAL ANTIGENIC SIN; ANTIBODY-DEPENDENT ENHANCEMENT; CLASS-I SUPERTYPES; HEMORRHAGIC-FEVER; MOUSE MODEL; SRI-LANKA; INFECTION; PATHOGENESIS; DISEASE; ALLELE;

D O I：

10.1073/pnas.1305227110

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：

The role of CD8(+) T cells in dengue virus infection and subsequent disease manifestations is not fully understood. According to the original antigenic sin theory, skewing of T-cell responses induced by primary infection with one serotype causes less effective response upon secondary infection with a different serotype, predisposing individuals to severe disease. A comprehensive analysis of CD8(+) responses in the general population from the Sri Lankan hyperendemic area, involving the measurement of ex vivo IFN gamma responses associated with more than 400 epitopes, challenges the original antigenic sin theory. Although skewing of responses toward primary infecting viruses was detected, this was not associated with impairment of responses either qualitatively or quantitatively. Furthermore, we demonstrate higher magnitude and more polyfunctional responses for HLA alleles associated with decreased susceptibility to severe disease, suggesting that a vigorous response by multifunctional CD8(+) T cells is associated with protection from dengue virus disease.

引用

页码：E2046 / E2053

页数：8

共 49 条

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