Escape of Human Immunodeficiency Virus from Immune Control

Cytotoxic T lymphocytes (CTL) play a crucial role in the attempt to control infection with human immunodeficiency virus (HIV). Variation in epitopes recognized by CTL is common and frequently offers potential escape routes for mutant virus. Proof of escape, however, requires demonstration of increased frequency of virus particles or provirus that carry the escape sequence. There are now several recorded examples of virus variants that escape from CTL and are then selected. Most dramatic are those in which the CTL response has been dominated by CTL recognizing a single epitope that has suddenly changed, resulting in escape to fixation. This has been seen both early and late in the infection, leaving no doubt that escape occurs. Such escape is likely to be favored when the antiviral CTL response is oligoclonal and focused on a small number of immunodominant epitopes. The heterogeneous CTL response seen in many HIV-infected patients may result from successive waves of virus escape followed by new CTL responses specific for subdominant epitopes. Mutant virus can escape by several different routes, including failure of the mutated peptide to bind to the presenting HLA molecule and altered interactions with T cell receptors (TCR), including antagonism.