Translational Neuroscience Seminar Series: Yoram Louzoun, PhD

08/16/2010 14:00
America/New York
Speaker: Yoram Louzoun
Professor, Department of Mathematics, Bar Ilan University, Israel

Venue: Annenberg 20-01
Mount Sinai Medical School

Title: Viruses and Bacteria selectively mutate their CD8+ T cell epitopes to modulate the immune response

Abstract:

Viruses employ various means to evade immune detection. One common evasion strategy is the removal of CD8+ cytotoxic T-lymphocyte (CTL) epitopes. We here use a combination of multiple bioinformatic tools and large amount of genomic data to compute the epitope repertoire presented by over 1,300 viruses in many HLA alleles as well as multiple bacteria. We define the "Size of Immune Repertoire (/SIR/) score," which represents the ratio between the epitope density within a protein and the expected density. This score is used to study viral immune evasion. We show that viral proteins in general have a higher epitope density than human proteins. This difference is due to a good fit of the human MHC molecules to the typical amino acid usage of viruses. Among different viruses, viruses infecting humans present less epitopes than non-human viruses. This selection is not at the amino acid usage level, but through the removal of specific epitopes. Within a single virus, not all proteins express the same epitopes density. Proteins expressed early in the viral life cycle or with a high copy number have a lower epitope density. We use HIV, HBV and Herpes viruses to show how viruses use their epitope repertoire to modulate the immune response. Surprisingly, the selection does not end at the level of viruses. Bacteria also modulate the epitope repertoire of proteins injected to the cytosol. They use these proteins to adapt the cellular immune system to their own needs.