Viruses employ various means to evade immune detection. One common evasion strategy is the removal of CD8+ T-lymphocyte epitopes. We use in-house epitope prediction algorithms for all stages of CTL epitope presentation (proteasomal cleavage, TAP binding and HLA binding) to build and analyze epitope repertoire of viruses and bacteria.
We have shown that viruses are systematically selected to remove their CTL epitopes, and that this selection is not uniform among proteins. More specifically, viruses favor the removal of epitopes in proteins that their hiding from the immune system will give the virus the best fitness benefit in terms of immune evasion. In this regard, we have shown that early expressed proteins (of Herpes viruses) and highly expressed proteins (of HBV) are under stronger selection against epitopes that late and low expressed proteins, respectively.
We have further shown that CTL evasion is not restricted to viruses. Although bacteria mainly controlled by B and CD4+ T-cells, some bacterial proteins reach the cytosol where they intersect with MHC-I pathway. This result in CTL mediated cell death and destruction of bacteria’s habitat. We have shown for the first time that as in viruses, escape mutations arise to avoid detection, are systematically present in bacteria.
We are now developing using machine learning a new generation of MHC epitope prediction algorithms.
Mutations in epitopes serve as an excellent real time model of evolution. We use these epitopes to test ecological and evolutionary models.