AntiJen: a quantitative immunology database integrating functional, thermodynamic, kinetic, biophysical, and cellular data

Abstract

AntiJen is a database system focused on the integration of kinetic, thermodynamic, functional, and cellular data within the context of immunology and vaccinology. Compared to its progenitor JenPep, the interface has been completely rewritten and redesigned and now offers a wider variety of search methods, including a nucleotide and a peptide BLAST search. In terms of data archived, AntiJen has a richer and more complete breadth, depth, and scope, and this has seen the database increase to over 31,000 entries. AntiJen provides the most complete and up-to-date dataset of its kind. While AntiJen v2.0 retains a focus on both T cell and B cell epitopes, its greatest novelty is the archiving of continuous quantitative data on a variety of immunological molecular interactions. This includes thermodynamic and kinetic measures of peptide binding to TAP and the Major Histocompatibility Complex (MHC), peptide-MHC complexes binding to T cell receptors, antibodies binding to protein antigens and general immunological protein-protein interactions. The database also contains quantitative specificity data from position-specific peptide libraries and biophysical data, in the form of diffusion co-efficients and cell surface copy numbers, on MHCs and other immunological molecules. The uses of AntiJen include the design of vaccines and diagnostics, such as tetramers, and other laboratory reagents, as well as helping parameterize the bioinformatic or mathematical in silico modeling of the immune system. The database is accessible from the URL: http://www.jenner.ac.uk/antijen.

Figure 1

The distribution of experimental methods applied within each database. The number of different experimental methods and the abundance of data relating to the method is shown within the figures. The 'OTHERS' category refers to methods for which there is a relatively small number of entries.

Figure 2

Overview of the different search methods within AntiJen. The example search is focused upon an MHC ligand. The MHC ligand data can be searched directly (A) from a link on the AntiJen homepage, a broad search and specific search is available. A search for the epitope AMALLRLPLV, has one hit (D), this leads to the entry (G). All of the other sub-databases can be searched in this manner from the homepage. The two other searches are more generalised. A Keyword search (B) carries out a broad search on the whole database, for the criteria – Bacteria. This search gives 139 hits (E) and all of the sub-database entries can be selected from this output. The final search method is a BLAST search (C). The peptide (or nucleotide) sequence is queried against a local protein database. The output (F) provides links to the sub-databases relative to the protein.

Figure 3

Searchable database types within AntiJen. The database contains 3 types of searchable sub database: a set of Antigens searchable by keyword, various databases of functional and thermodynamic data searchable by peptide sequence, and a database of immunological protein-protein interactions searchable through an index. Peptide sequence searches can be explicit or "motif" based. Searches can also be focussed by setting the value ranges for properties, such as IC₅₀ etc, recorded in the databases. Currently there is a link between all the thermodynamic and kinetic databases and between them and the database of antigens. Only antigens with data in one of the other sub-databases are included in the antigen database. Links to external databases are also indicated. The BLAST search provides an overall search of the databases except the Protein-Protein Interactions archive.

Figure 4

Sparse peptide sequence search. Examples of the two search types available in AntiJen: (Search 1) a substring query and (Searches 2 and 3) PROSITE-like sparse queries allowing sets of variable (indicated by asterisks) and alternative (encased in square brackets) amino acids in the search. In our example, each query is an extension of the previous search. The initial search type returns a single hit, which is a weak binder. By introducing variable amino acid positions within the query string, the second query permits access to a larger data set with 39 hits being returned. The third search utilises both variable and alternative amino acid request functionality and returns 1996 hits. The number of entries returned can be reduced by specifying the epitope length, limiting IC₅₀ values and restricting by one MHC allele. This search is constrained to peptides of amino acid length 9, which returns 280 hits. Constraining further by MHC allele HLA-A*0201, reduces this to 120. An additional constraint using the IC50 data filter, and requesting values below 500 only (the epitope range), reduces this again to 60.