Title | ||
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Prediction of class I T-cell epitopes: evidence of presence of immunological hot spots inside antigens |
Abstract | ||
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Motivation: Processing and presentation of major histocompatibility complex class I antigens to cytotoxic T-lymphocytes is crucial for immune surveillance against intracellular bacteria, parasites, viruses and tumors. Identification of antigenic regions on pathogen proteins will play a pivotal role in designer vaccine immunotherapy. We have developed a system that not only identifies high binding T-cell antigenic epitopes, but also class I T-cell antigenic clusters termed immunological hot spots. Methods: MULTIPRED, a computational system for promiscuous prediction of HLA class I binders, uses artificial neural networks (ANN) and hidden Markov models (HMM) as predictive engines. The models were rigorously trained, tested and validated using experimentally identified HLA class I T-cell epitopes from human melanoma related proteins and human papillomavirus proteins E6 and E7. We have developed a scoring scheme for identification of immunological hot spots for HLA class I molecules, which is the sum of the highest four predictions within a window of 30 amino acids. Results: Our predictions against experimental data from four melanoma-related proteins showed that MULTIPRED ANN and HMM models could predict T-cell epitopes with high accuracy. The analysis of proteins E6 and E7 showed that ANN models appear to be more accurate for prediction of HLA-A3 hot spots and HMM models for HLA-A2 predictions. For illustration of its utility we applied MULTIPRED for prediction of promiscuous T-cell epitopes in all four SARS coronavirus structural proteins. MULTIPRED predicted HLA-A2 and HLA-A3 hot spots in each of these proteins. |
Year | DOI | Venue |
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2004 | 10.1093/bioinformatics/bth943 | ISMB/ECCB (Supplement of Bioinformatics) |
Field | DocType | Volume |
Epitope,Antigen,Biology,Major histocompatibility complex,SARS coronavirus,Immune system,Cytotoxic T cell,Bioinformatics,Human leukocyte antigen,Intracellular parasite | Conference | 20 |
Issue | ISSN | Citations |
1 | 1367-4803 | 9 |
PageRank | References | Authors |
1.50 | 4 | 5 |
Name | Order | Citations | PageRank |
---|---|---|---|
K.N. Srinivasan | 1 | 9 | 1.50 |
G.L. Zhang | 2 | 208 | 16.91 |
A.M. Khan | 3 | 9 | 1.50 |
J.T. August | 4 | 9 | 1.50 |
V. Brusic | 5 | 11 | 2.50 |