ESCAPE OF HUMAN-IMMUNODEFICIENCY-VIRUS FROM IMMUNE CONTROL

Cytotoxic T lymphocytes (CTL) play a crucial role in the attempt to co ntrol infection with human immunodeficiency virus (HIV). Variation in epitopes recognized by CTL is common and frequently offers potential e scape routes for mutant virus. Proof of escape, however, requires demo nstration of increased frequency of virus particles or provirus that c arry the escape sequence. There are now several recorded examples of v irus variants that escape from CTL and are then selected. Most dramati c are those in which the CTL response has been dominated by CTL recogn izing 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 favor ed when the antiviral CTL response is oligoclonal and focused on a sma ll number of immunodominant epitopes. The heterogeneous CTL response s een in many HIV-infected patients may result from successive waves of virus escape followed by new CTL responses specific for subdominant ep itopes. 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 antag onism.