The Use of the Immune Epitope Database to Study Autoimmune Epitope Data Related to Alopecia Areata

Abstract

The Immune Epitope Database (IEDB) is a repository of published epitope data for infectious diseases, allergy, transplantation and autoimmunity. Herein we provide an introduction to the IEDB search interface, focusing on data related to autoimmune diseases, including alopecia areata (AA). We demonstrate how common questions related can be answered, such as how to search for specific autoantigens, epitope sequences, response types (B- and/or T-cell assays), or host, as well as how to search for epitopes of known major histocompatibility complex restriction and for data related to a specific disease. Our survey of the data found that while as a whole Autoimmunity-specific records represent a significant portion (∼30%); epitopes reported for AA are remarkably few, just 23 epitopes from six antigens. This reveals a significant knowledge gap for AA, and suggests that additional mapping of epitopes and identification of novel AA-associated autoantigens is warranted. Citing recently published examples, we show how bioinformatic, proteomic, and technological advances make it now increasingly feasible to identify epitopes and novel antigens in human disease. The goal herein was to increase awareness of the IEDB as a free resource for the scientific community and to demonstrate its use in finding (existing) and analyzing (prediction) epitope data.

Figure 1.. Immune Epitope Database (IEDB) Search Interface.

A screen shot showing the main search interface on IEDB.org. The interface is comprised of six main “search panes,” epitope, antigen, assay, major histocompatibility complex (MHC) restriction, host and disease, which allow the user to select specific criteria pertaining to the nature of the epitope(s) of interest (e.g., linear T-cell epitopes from protein X) or to limit their query to certain subsets of the cumulative data (e.g., particular host with disease).

Figure 2.. Results summary page for “alopecia areata” query.

The Results page is generated from any query initiated on the Immune Epitope Database (IEDB) home page. Query results are presented on a tab delineated table located centrally on this page. On the Results table there are four tabs: (i) epitopes, (ii) antigens, (iii) assays, and (iv) references. Each tab shows in parentheses the total number of records from the latest query and can be clicked open to reveal data details (by row or column). Clicking on rows within a tab allows access to all details of the experiments captured within. If the user wishes to change or refine an ongoing query, search panes located along the left-hand side on this page are provided. Queries performed on this page are nearly limitless, as access to all database fields is provided.

Figure 3.. Results page assay tab opened showing the content and organization of data by columns and rows.

Here, the assay tab of the results table has been clicked open to reveal the overall content and organization of the assay-specific data. Note the smaller tabs present at the top summarize data for all response types, T-cell assays, B-cell assays, and major histocompatibility complex (MHC) ligand assays (if present/reported) with the totals shown in parentheses. Below, the data are organized into nine columns: assay ID, reference, epitope, host, immunization, assay antigen, antigen epitope relation, MHC restriction and assay description, providing a quick snap shot of the individual records. Clicking on any row will allow the user to “drill down” into each record to see details of the experimental process and outcome. The entire set of T-cell assays shown in this query (as an example) could be downloaded in Excel by clicking the Excel (Microsoft, Redmond, WA) icon in the top right corner.

Figure 4.. The Immune Epitope Database (IEDB) analysis resource.

The IEDB analysis resource is an integrated part of the epitope database and provides T-cell epitope prediction, B-cell epitope prediction, as well as other epitope analysis tools, including population coverage, conservation across antigens, clusters with similar sequences, location in three-dimensional (3D) structure. (a) The analysis resource menu located on the right side of the IEDB home page. (b) The T-cell prediction tool menu opened to highlight available methods.