An analysis of the epitope knowledge related to Mycobacteria
Immunome Research
An analysis of the epitope knowledge related to Mycobacteria
Martin J Blythe 2
Qing Zhang 2
Kerrie Vaughan 2
Romulo de Castro Jr 2
Nima Salimi 2
Huynh-Hoa Bui 2
David M Lewinsohn 1
Joel D Ernst 0
Bjoern Peters 2
Alessandro Sette 2
0 Division of Infectious Diseases, New York University School of Medicine , 550 First Avenue, Smilow 901, New York, 10016 , USA
1 Portland VA Medical Center/Oregon Heath and Science University , R&D 11, PVAMC, 3710 SW US Veterans Road, Portland, Oregon, 97239 , USA
2 Department of Vaccine Discovery, La Jolla Institute for Allergy and Immunology , 9420 Athena Circle, La Jolla, California, 92037 , USA
Background: Tuberculosis, caused by the bacterium Mycobacterium tuberculosis, remains a leading cause of infectious disease morbidity and mortality, and is responsible for more than 2 million deaths a year. Reports about extremely drug resistant (XDR) strains have further heightened the sense of urgency for the development of novel strategies to prevent and treat TB. Detailed knowledge of the epitopes recognized by immune responses can aid in vaccine and diagnostics development, and provides important tools for basic research. The analysis of epitope data corresponding to M. tuberculosis can also identify gaps in our knowledge, and suggest potential areas for further research and discovery. The Immune Epitope Database (IEDB) is compiled mainly from literature sources, and describes a broad array of source organisms, including M. tuberculosis and other Mycobacterial species. Description: A comprehensive analysis of IEDB data regarding the genus Mycobacteria was performed. The distribution of antibody/B cell and T cell epitopes was analyzed in terms of their associated recognition cell type effector function and chemical properties. The various species, strains and proteins which the epitope were derived, were also examined. Additional variables considered were the host in which the epitopes were defined, the specific TB disease state associated with epitope recognition, and the HLA associated with disease susceptibility and endemic regions were also scrutinized. Finally, based on these results, standardized reference datasets of mycobacterial epitopes were generated. Conclusion: All current TB-related epitope data was cataloged for the first time from the published literature. The resulting inventory of more than a thousand different epitopes should prove a useful tool for the broad scientific community. Knowledge gaps specific to TB epitope data were also identified. In summary, few non-peptidic or post-translationally modified epitopes have been defined. Most importantly epitopes have apparently been defined from only 7% of all ORFs, and the top 30 most frequently studied protein antigens contain 65% of the epitopes, leaving the majority of M. tuberculosis genome unexplored. A lack of information related to the specific strains from which epitopes are derived is also evident. Finally, the generation of reference lists of mycobacterial epitopes should also facilitate future vaccine and diagnostic research.
Background
The goal of the Immune Epitope Database and Analysis
Resource (IEDB) [1] is to compile epitope-specific
immunological data, as well as analysis tools, and to facilitate
the characterization of immune responses in humans and
other higher vertebrates. Epitope information can be
useful to the scientific community in the design,
characterization, and identification of potential vaccines and
diagnostics, as well as to assist in basic investigation of
immune responses and host-pathogen interactions. In
terms of the type of immune responses and associated
epitopes considered, we describe epitopes recognized in
the context of the adaptive immune response, namely
antibody/B and T cell epitopes. Each type of epitope is
defined as the molecular structure that is bound by an
antibody or T cell receptor.
Curation of data relating to NIAID Category A, B, and C
pathogens [2], emerging and re-emerging infectious
diseases and various other pathogens into the IEDB is current
with the published literature (see [1] for a current list). To
date, the database describes epitopes sourced from over
4,000 publications detailing in excess of 32,000 distinct
epitopes. Besides epitopes composed of amino acids, the
IEDB includes information from all other chemical classes
of non-peptidic antigens, including lipids, glycolipids,
carbohydrates, DNA, RNA, and small organic molecules.
The information can be searched using multiple
parameters. For each epitope, specific fields summarize
immunological data, including detailed information related to the
immunized/infected host organism and source of the
antigenic determinant. Associated fields also describe the
experimental techniques used to characterize the epitope,
and the immunological response detected [
3,4
]. The IEDB
also hosts various bioinformaticstools to analyze epitope
data, including: populationcoverage [
5
]; ep (...truncated)