Immunogenetics & HLA
HLA nomenclature
Chromosome 6
Proteasome Predictions
NetChop
MAPPP
PAPROC
MHC Motif Descriptions
& Binding Predictions
FIMM
(previously MCHPEP http://wehih.wehi.edu.au/mhcpep/)
NetMHC
HLA Ligand & Motifs
BIMAS
SYFPEITHY
Tetramers
Tetramer Facility
Soeren Buus, MD, PhD - Chair
Analysis and predictions of the events involved in antigen processing and presentation
The goal of the Peptide Component is to provide detailed descriptions of antigen processing and presentation, to develop accurate predictions of these events, and to apply these to the identification of immunogenic epitopes. The short-term goal is to generate the tools and methods needed to analyze the specificities involved in particular those of the most prevalent MHC molecules. We have generated "empty" recombinant HLA class I molecules (at this time HLA-A*0101, -A*0201, A*0301 and A*1101) of peptide binding quality and developed the corresponding peptide binding assays. We are currently implementing a quantitative ELISA-based assay for measuring peptide-MHC interactions. The aim is to disseminate the protocols, reagents and standards that will allow interested laboratories to generate and measure peptide-MHC complexes of their own choice.
We are analyzing the peptide binding specificity of the HLA class I molecules using several complementing approaches. HLA class I molecules are purified from natural sources, bound peptides are eluted off, and individual peptides as well as motifs are identified by peptide sequencing. In parallel, we are using synthetic peptide and peptide libraries in conjunction with biochemical assays like the above ELISA to generate quantitative data on peptide-HLA binding. These efforts will lead to a detailed, unbiased description of the peptide binding motifs of the most common HLA molecules.
The above data - representing the specificity of the HLA molecules and examples of peptide-HLA interactions - are used to train artificial neural networks (ANN) to perform quantitative predictions of peptide binding to HLA. Similarly, predictions of other events involved i.e. such as proteasomal processing will also be developed and integrated with those of HLA binding. All of these predictions are computerized and can readily be applied to genomic and proteomic information thereby enabling a rapid search for immunogenic epitopes from the entire proteomes of pathogenic organisms.
The long-term goal is to include all events involved in antigen processing and presentation, and to cover all human HLA molecules. The implications are far reaching. Complete genomes of many species including pathogenic micro-organisms are rapidly becoming available and with them the encoded proteins, or proteomes.. The ability to translate the accumulating primary sequence databases in terms of immune recognition should enable scientists and clinicians to analyze any protein of interest for the presence of potentially immunogenic epitopes. This should enable a rational approach to vaccine development and immunotherapy. Thus, candidate vaccine epitopes might be predicted from the various microbial genome projects, tumor vaccine candidates from mRNA expression profiling of tumors (''transcriptomes'') and auto-antigens from the human genome.
Laboratories possessing data on the specificity of antigen processing and presentation, and laboratories interested in generating data in this area, are encouraged to join the effort. Protocols and prediction will be made available. Reagents and standards will be made available on a limited basis.
Soeren Buus, Professor, MD, PhD
Institute for Medical Microbiology and Immunology
Panum 18.3.22
Blegdamsvej 3
DK-2200 Copenhagen N
Denmark
45-3532-7885
45-3532-7853 (fax)
s.buus@immi.ku.dk
