DYNAMICS OF T-CELL ANTAGONISM - ENHANCED VIRAL DIVERSITY AND SURVIVAL

In rapidly evolving viruses tile detection of virally infected cells c an possibly be subverted by the production of altered peptides. These are peptides with single amino acid changes that can dramatically chan ge T-cell responses, e.g. a loss of cytotoxic activity. They are still recognized by the T cell, but the signals required for effector funct ion are only partially delivered. Thus, altered peptide presenting cel ls can act as decoy targets for specific immune responses. The existen ce of altered peptides in vivo has been demonstrated in hepatitis B an d HIV. Using a mathematical model we address the question of how these altered peptides can affect the virus-immune system dynamics, and dem onstrate that virus survival is enhanced. If the mutation rate of the virus is sufficient, one observes complex dynamics in which the antago nism acts so as to maintain the viral diversity, possibly leading to t he development of a mutually antagonistic network or a continual turno ver of escape mutants. In either case the pathogen is able to outrun t he immune system. Indeed, sometimes the enhancement is so great that a virus that would normally be cleared by the immune system is able to outrun it.