TY - JOUR

T1 - Identifying cytotoxic T cell epitopes from genomic and proteomic information: "The human MHC project."

AU - Lauemøller, S L

AU - Kesmir, C

AU - Corbet, S L

AU - Fomsgaard, A

AU - Holm, Arne

AU - Claesson, M H

AU - Brunak, S

AU - Buus, S

N1 - Keywords: Antigen Presentation; Epitopes; Genome; Histocompatibility Antigens Class I; Humans; Immunogenetics; Major Histocompatibility Complex; Models, Molecular; Neural Networks (Computer); Peptide Library; Polymorphism, Genetic; Protein Binding; Proteome; T-Lymphocytes, Cytotoxic; T-Lymphocytes, Helper-Inducer; Vaccines

PY - 2000

Y1 - 2000

N2 - Complete genomes of many species including pathogenic microorganisms are rapidly becoming available and with them the encoded proteins, or proteomes. Proteomes are extremely diverse and constitute unique imprints of the originating organisms allowing positive identification and accurate discrimination, even at the peptide level. It is not surprising that peptides are key targets of the immune system. It follows that proteomes can be translated into immunogens once it is known how the immune system generates and handles peptides. Recent advances have identified many of the basic principles involved. The single most selective event is that of peptide binding to MHC, making it particularly important to establish accurate descriptions and predictions of peptide binding for the most common MHC variants. These predictions should be integrated with those of other steps involved in antigen processing, as these become available. 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. The computational tools to scan entire proteomes should also be developed, as this would 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.

AB - Complete genomes of many species including pathogenic microorganisms are rapidly becoming available and with them the encoded proteins, or proteomes. Proteomes are extremely diverse and constitute unique imprints of the originating organisms allowing positive identification and accurate discrimination, even at the peptide level. It is not surprising that peptides are key targets of the immune system. It follows that proteomes can be translated into immunogens once it is known how the immune system generates and handles peptides. Recent advances have identified many of the basic principles involved. The single most selective event is that of peptide binding to MHC, making it particularly important to establish accurate descriptions and predictions of peptide binding for the most common MHC variants. These predictions should be integrated with those of other steps involved in antigen processing, as these become available. 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. The computational tools to scan entire proteomes should also be developed, as this would 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.

M3 - Journal article

C2 - 12361091

VL - 2

SP - 477

EP - 491

JO - Reviews in Immunogenetics

JF - Reviews in Immunogenetics

SN - 1398-1714

IS - 4

ER -