Memory T Cells in Latent Mycobacterium tuberculosis Infection Are Directed against Three Antigenic Islands and Largely Contained in a CXCR3+CCR6+ Th1 Subset

被引：194

作者：

Arlehamn, Cecilia S. Lindestam ^{[1
]}

Gerasimova, Anna ^{[1
]}

Mele, Federico ^{[2
]}

Henderson, Ryan ^{[1
]}

Swann, Justine ^{[1
]}

Greenbaum, Jason A. ^{[1
]}

Kim, Yohan ^{[1
]}

Sidney, John ^{[1
]}

James, Eddie A. ^{[3
]}

Taplitz, Randy ^{[4
]}

McKinney, Denise M. ^{[1
]}

Kwok, William W. ^{[3
]}

Grey, Howard ^{[1
]}

Sallusto, Federica ^{[2
]}

Peters, Bjoern ^{[1
]}

Sette, Alessandro ^{[1
]}

机构：

[1] La Jolla Inst Allergy & Immunol, La Jolla, CA USA

[2] Inst Res Biomed, Bellinzona, Switzerland

[3] Benaroya Res Inst, Seattle, WA USA

[4] Univ Calif San Diego, Antiviral Res Ctr, San Diego, CA 92103 USA

来源：

PLOS PATHOGENS | 2013年 / 9卷 / 01期

基金：

瑞士国家科学基金会; 美国国家卫生研究院;

关键词：

POLYFUNCTIONAL CD4(+); ESAT-6; FAMILY; VACCINE; PROTEINS; GENE; EXPRESSION; RESPONSES; CYTOKINE; SECRETION; HELPER;

D O I：

10.1371/journal.ppat.1003130

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

An understanding of the immunological footprint of Mycobacterium tuberculosis (MTB) CD4 T cell recognition is still incomplete. Here we report that human Th1 cells specific for MTB are largely contained in a CXCR3(+)CCR6(+) memory subset and highly focused on three broadly immunodominant antigenic islands, all related to bacterial secretion systems. Our results refute the notion that secreted antigens act as a decoy, since both secreted proteins and proteins comprising the secretion system itself are targeted by a fully functional T cell response. In addition, several novel T cell antigens were identified which can be of potential diagnostic use, or as vaccine antigens. These results underline the power of a truly unbiased, genome-wide, analysis of CD4 MTB recognition based on the combined use of epitope predictions, high throughput ELISPOT, and T cell libraries using PBMCs from individuals latently infected with MTB.

引用

页数：16

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