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

Immunome Research BioMed Central Database Open Access AntiJen: a quantitative immunology database integrating functional, thermodynamic, kinetic, biophysical, and cellular data Christopher P Toseland†, Debra J Clayton†, Helen McSparron†, Shelley L Hemsley, Martin J Blythe, Kelly Paine, Irini A Doytchinova, Pingping Guan, Channa K Hattotuwagama and Darren R Flower* Address: Edward Jenner Institute for Vaccine Research, High Street, Compton, Berkshire, RG20 7NN, UK Email: Christopher P Toseland - ; Debra J Clayton - ; Helen McSparron - ; Shelley L Hemsley - ; Martin J Blythe - ; Kelly Paine - ; Irini A Doytchinova - ; Pingping Guan - ; Channa K Hattotuwagama - ; Darren R Flower* - * Corresponding author †Equal contributors Published: 06 October 2005 Immunome Research 2005, 1:4 doi:10.1186/1745-7580-1-4 Received: 17 June 2005 Accepted: 06 October 2005 This article is available from: http://www.immunome-research.com/content/1/1/4 © 2005 Toseland et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. B Cell EpitopesMHC-peptide bindingT Cell EpitopesMHCTCRAntibodiesVaccines 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. Introduction There is a vast, and ever increasing, volume of important information that has accumulated from decades of exper- imental analysis within immunology. This will only become compounded as high-throughput techniques begin to impinge upon the immunological biosciences. Page 1 of 12 (page number not for citation purposes) Immunome Research 2005, 1:4 The only efficient way for this information to be properly utilized requires the development of databases that store it and systems that use it. Although the type of data archived may alter from case to case, nonetheless the creation, use, and manipulation of databases containing biologically important information is the most crucial feature of current bioinformatics, both as it supports the genomic and post-genomic revolutions and as a discipline in its own right. There is nothing new in developing databases focusing on immunology: many spotlighting the in-depth sequence analysis of individual immunomacromolecules have existed for some time [1]. Functional or epitope-orientated databases are a more recent development. Examples include the now defunct MHCPEP database [2]http:/ /wehih.wehi.edu.au/mhcpep/, FIMM [3]http:// sdmc.krdl.org.sg:8080/fimm, SYFPEITHI [4]http:// www.syfpeithi.de, the HIV sequence database [5]http:// hiv-web.lanl.gov/, the HLA ligand database [6]http://hla ligand.ouhsc.edu, the EPIMHC database [7]http:// bio.dfci.harvard.edu/epimhc/, and the MHCBN database [8]http://www.imtech.res.in/raghava/mhcbn/. An epitope is any molecular structure that can be recognised by the immune, or other biological, system. Epitopes, or the antigen from which they are derived, can be composed of protein, carbohydrate, lipid, nucleotide, or a combination thereof. It is through recognition of foreign, or non-self, epitopes that the immune system can identify and, hopefully, destroy pathogens. Hitherto, peptide epitopes have been the best studied, and have, traditionally, have been categorized as either T cell or B cell epitopes. T cell epitopes are peptides presented to the cellular arm of the immune system via the MHC-peptideTCR complex. B cell epitopes represent surface regions of an antigen that are bound by soluble or membranebound antibodies. If this region of a protein antigen is comprised of residues distally separated within the primary structure, and brought into local proximity by protein folding, then it is termed a discontinuous or conformational B cell epitope. Linear or continuous B cell epitope residues are sequential in both primary structure and thus as a region on the proteins' surface. Such epitopes are predominantly identified by antigen-specific antibody cross-reactivity with peptides. There is a need to create a databank for the wider disciplines of immuno-vaccinologists, which can act as a central repository and resource. Our aim is to complement other databanks [2-8] and thus we have developed AntiJen, a computational information resource for immunology and vaccinology that integrates quantitative kinetic, thermodynamic and biophysical data, with functional and cellular information. AntiJen v2.0, a development of our earlier database system JenPep [9,10], contains functional data on T cell and B cell epitopes. Moreover, the B http://www.immunome-research.com/content/1/1/4 cell archive is now sub-divided into linear and conformational epitopes. These epitopes form the basis of the humoral immune response and, unlike T cell epitopes, methods of prediction are often inaccurate [11]. A more in-depth B cell epitope archive should aid the development of prediction strategies. Antigen recognition by the Major Histocompatibility Complex (MHC) is vital to T cell activation hence, the inclusion of thermodynamic data on the binding of peptides to MHC molecules and T Cell Receptor (TCR) binding to peptide-MHC (pMHC) complexes. This data is complemented by kinetic data based on the same molecular interactions. Data on antigen processing and presentation is also included in AntiJen. Binding data derived from peptide (...truncated)