AffiliationSchool of Mathematics, Statistics and Applied Mathematics, National University of Ireland, Galway, Ireland.
HIV Core Protein p24
MetadataShow full item record
CitationEpitope discovery with phylogenetic hidden Markov models. 2010, 27 (5):1212-20 Mol. Biol. Evol.
JournalMolecular biology and evolution
AbstractExisting methods for the prediction of immunologically active T-cell epitopes are based on the amino acid sequence or structure of pathogen proteins. Additional information regarding the locations of epitopes may be acquired by considering the evolution of viruses in hosts with different immune backgrounds. In particular, immune-dependent evolutionary patterns at sites within or near T-cell epitopes can be used to enhance epitope identification. We have developed a mutation-selection model of T-cell epitope evolution that allows the human leukocyte antigen (HLA) genotype of the host to influence the evolutionary process. This is one of the first examples of the incorporation of environmental parameters into a phylogenetic model and has many other potential applications where the selection pressures exerted on an organism can be related directly to environmental factors. We combine this novel evolutionary model with a hidden Markov model to identify contiguous amino acid positions that appear to evolve under immune pressure in the presence of specific host immune alleles and that therefore represent potential epitopes. This phylogenetic hidden Markov model provides a rigorous probabilistic framework that can be combined with sequence or structural information to improve epitope prediction. As a demonstration, we apply the model to a data set of HIV-1 protein-coding sequences and host HLA genotypes.
CollectionsJournal articles & published research
- Prediction of class I T-cell epitopes: evidence of presence of immunological hot spots inside antigens.
- Authors: Srinivasan KN, Zhang GL, Khan AM, August JT, Brusic V
- Issue date: 2004 Aug 4
- Selection, transmission, and reversion of an antigen-processing cytotoxic T-lymphocyte escape mutation in human immunodeficiency virus type 1 infection.
- Authors: Allen TM, Altfeld M, Yu XG, O'Sullivan KM, Lichterfeld M, Le Gall S, John M, Mothe BR, Lee PK, Kalife ET, Cohen DE, Freedberg KA, Strick DA, Johnston MN, Sette A, Rosenberg ES, Mallal SA, Goulder PJ, Brander C, Walker BD
- Issue date: 2004 Jul
- Genetic variability of hepatitis C virus non-structural protein 3 and virus-specific CD8+ response in patients with chronic hepatitis C.
- Authors: López-Labrador FX, He XS, Berenguer M, Cheung RC, González-Candelas F, Wright TL, Greenberg HB
- Issue date: 2004 Apr
- The flexibility of the TCR allows recognition of a large set of naturally occurring epitope variants by HIV-specific cytotoxic T lymphocytes.
- Authors: Buseyne F, Rivière Y
- Issue date: 2001 Jul
- Loss of HIV-1-derived cytotoxic T lymphocyte epitopes restricted by protective HLA-B alleles during the HIV-1 epidemic.
- Authors: Schellens IM, Navis M, van Deutekom HW, Boeser-Nunnink B, Berkhout B, Kootstra N, Miedema F, Keşmir C, Schuitemaker H, van Baarle D, Borghans JA
- Issue date: 2011 Sep 10