Rich Epitope Information Comes to UniProt
Mammalian immune responses are mediated by interactions between antigens and
immune system components such as antibodies, B cells, and T cells. However,
antibodies and immune cells do not bind to entire antigens, which are usually
proteins or large polysaccharides; instead, they recognize one or more small
regions within the antigen called epitopes. Characterizing epitopes gives us
insight into infectious diseases, autoimmune diseases, and cancer,
and leads to therapeutic innovations such as the development of more effective
vaccines.
UniProt curators have traditionally included information about protein epitopes
from the literature as part of the process of manually annotating protein entries.
However, epitope information in UniProt recently got a big boost from a
collaboration with the Immune Epitope Database (IEDB). The IEDB is a
freely available, manually curated resource that catalogs experimental data
on antibody and T cell epitopes in humans and other animal species in
the context of a variety of diseases and conditions.
Thanks to the UniProt-IEDB collaboration, epitopes curated by the IEDB can be viewed
in a track in the UniProt Feature Viewer with links back to the IEDB. In addition,
publications with epitope information identified by the IEDB are now accessible on UniProt
Publications pages, and IEDB epitopes are searchable using the Proteins API.
The collaboration has enhanced UniProt with information about more than 700,000
naturally occurring, linear peptide epitopes in over 57,000 proteins, citing over 7,000 papers that describe their experimental characterization.
For example, consider the protein O-phosphoseryl-tRNA(Sec) selenium transferase
(SEPSECS; UniProt ID: Q9HD40). SEPSECS (aka SLA/LP autoantigen), which
normally functions as an enzyme in selenoprotein biosynthesis, is an autoantigen in
autoimmune hepatitis (AIH), a chronic inflammatory disease of the liver. Patients
with AIH have circulating antibodies against SEPSECS as well as lymphocyte
infiltrations in the liver. The UniProt entry page identifies the region from amino acids
474-493 as an SLA/LP epitope based on UniProt curation of a publication
characterizing autoantibodies in AIH (PMID:11826415; top panel of figure). The
Epitopes track of the Feature Viewer (middle panel of figure) displays the epitopes of
SEPSECS that have been curated by the IEDB, aligned with their positions in the
protein sequence. Clicking on an epitope brings up a box with the epitope sequence,
the experiments in which the epitope was studied, and a link to the epitope’s page in IEDB.
Finally, the Publications page (bottom panel of figure) lists a paper with epitope
information that was cited by IEDB (PMID:18773898). According to the accompanying
annotation, SEPSECS is a target of T cells in patients with AIH. A review of the abstract
reveals that the paper describes the identification of multiple epitopes in SEPSECS that
are recognized by autoreactive CD4+ T cells in AIH.
The inclusion of epitope and related immune information from IEDB in UniProt is an
exciting development that will hopefully prove valuable to immunologists and others
interested in the role of the immune system in health and disease.
