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

PLoS Pathogens

Randy Taplitz¹  Eddie A. James²  William W. Kwok²  Federica Sallusto³  Federico Mele³  Jason A. Greenbaum⁴  Alessandro Sette⁴  Howard Grey⁴  Cecilia S. Lindestam Arlehamn⁴  Denise M. McKinney⁴  Bjoern Peters⁴  John Sidney⁴  Ryan Henderson⁴  Justine Swann⁴  Yohan Kim⁴  Anna Gerasimova⁴ 

[1] Antiviral Research Centre, University of California, San Diego, San Diego, California, United States of America;Benaroya Research Institute, Seattle, Washington, United States of America;Institute for Research in Biomedicine, Bellinzona, Switzerland;La Jolla Institute for Allergy and Immunology, La Jolla, California, United States of America

关键词: T cells;    Mycobacterium tuberculosis;    Isl;    s;    Memory T cells;    Antigen processing;    recognition;    T helper cells;    Antigens;    Immune response;   

DOI  :  10.1371/journal.ppat.1003130

学科分类：生物科学（综合）

来源: Public Library of Science

【 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.

【 授权许可】

CC BY