MaPS Research Data

UMMS Affiliation

Department of Microbiology and Physiological Systems

Document Type

Data

File Format & Size

.xlsx (14MB)

Publication Date

4-7-2015

Funders

National Institute of Allergy and Infectious Diseases, National Institutes of Health, U.S. Department of Health and Human Services

Grant Number

R01 AI106725

Keywords

Mycobacterium tuberculosis, Tuberculosis, Tuberculosis vaccines, CD8+ T cells, T cell receptors, immunodominance

Description

Manuscript abstract: The immune system can recognize virtually any antigen, yet T cell responses against several pathogens, including Mycobacterium tuberculosis, are restricted to a limited number of immunodominant epitopes. The host factors that affect immunodominance are incompletely understood. Whether immunodominant epitopes elicit protective CD8+ T cell responses or instead act as decoys to subvert immunity and allow pathogens to establish chronic infection is unknown. Here we show that anatomically distinct human granulomas contain clonally expanded CD8+ T cells with overlapping T cell receptor (TCR) repertoires. Similarly, the murine CD8+ T cell response against M. tuberculosis is dominated by TB10.44-11-specific T cells with extreme TCRβ bias. Using a retrogenic model of TB10.44-11-specific CD8+ T cells, we show that TCR dominance can arise because of competition between clonotypes driven by differences in affinity. Finally, we demonstrate that TB10.4-specific CD8+ T cells mediate protection against tuberculosis, which requires interferon-γ production and TAP1-dependent antigen presentation in vivo. Our study of how immunodominance, biased TCR repertoires, and protection are inter-related, provides a new way to measure the quality of T cell immunity, which if applied to vaccine evaluation, could enhance our understanding of how to elicit protective T cell immunity.

Data Collection Start Date

2014

Data Collection End Date

2015

Methodology

Methodology is documented in published manuscript.

Publisher

eScholarship@UMMS

Language

eng

Code Lists

See Additional File that contains an explanation of the data fields in the spreadsheet.

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.

immunoSEQ_Codel.pdf (224 kB)
Code list information for dataset

.xlsx (14MB)

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