Predicting the Interplay of Epitope Recognition and Evolution in RNA Viruses Under Immune Pressure
Abstract
RNA viruses can rapidly mutate, causing therapeutics and vaccines to loose their effectiveness. The long-term goal of this project is to predict such mutations, in order to anticipate their effect and design better therapeutics and vaccines. In the funding period reported here, the specific goal was to build a predictive model of viral escape from immune pressure exerted by monospecific T cells in vitro. This goal was achieved: a general model was developed that integrates selective pressure determined by the phenotype of a virus with random mutations at the genotype level. To make quantitative predictions, the model requires parameters characterizing the selective pressure. These were determined experimentally for the specific case of T cell recognition of the LCM virus epitope NP 396 - 404. The parameterized model was shown to agree with escape mutants reported to arise when co-culturing the virus with these epitope-specific T cells.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 30, 2008
- Accession Number
- ADA500852
Entities
People
- Alesandro Sette
- Bjoern Peters
- Martin Blythe
Organizations
- La Jolla Institute for Allergy and Immunology