CD8 memory, immunodominance, and antigenic escape.
Previous theoretical work has suggested that efficient virus control or clearance requires antigen-independent persistence of memory cytotoxic T lymphocyte precursors (CTLp), and that failure to generate such memory CTLp can result in persistent infection and eventual loss of virus control. Here we use mathematical models to investigate the relationship between virus control, the clonal composition of the CTL response and the chance of the virus to evolve antigenic escape. In the presence of efficient memory CTLp, virus is controlled at very low levels by a broad CTL response directed against multiple epitopes. In this case, antigenic escape of the virus population is expected to take a very long time. On the other hand, if the CTL response is short lived in the absence of antigen, virus replicates at higher levels and is only opposed by a narrow CTL response, characterized by an immunodominant CTL clone. In this case, antigenic escape is expected to evolve in a short period of time, resulting in progressive loss of virus control. We discuss our findings in relation to data from HIV-1-infected patients.
Wodarz
D
D
Institute for Advanced Study, Princeton, NJ 08540, USA.
Nowak
M A
MA
D000939:Epitopes; D006412:Hematopoietic Stem Cells / Q000276:immunology; D006801:Humans; D007156:Immunologic Memory; D008433:Mathematics; D008954:Models, Biological; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014777:Virus Diseases / Q000276:immunology*; D014779:Virus Replication
D000939:Epitopes