(From Abstract) Despite vigorous CTL responses, HIV-1 infection usually leads to disease progression in the majority of infected individuals. The mechanisms responsible for viral persistence and failure of the cellular immune response remain mechanisms by which HIV-1 may elude the host cytolytic response, specifically: (a) the role of virologic factors in escaping recognition by CTL (sequence variation leading to nonrecognition and use of accessory genes to escape immune recognition), (b) the ability of CTL to suppress HIV-1 replication in various primary cell types (including non-lymphocytic cells susceptible to infection), and (c) the phenotype and function of HIV-1-specific CTL from bulk CD8+ cells in infected individuals. A previously established experimental system will be utilized for these studies. In general, acutely infected transformed CD4+ cell lines will cocultured with HLA-matched HIV-1 CTL clones. Manipulation of individual components of this experimental system will be employed to analyze specific factors that may affect the ability of CTL to suppress HIV-1 replication. Variation of the virus used for infection of the target cells will allow examination of virologic factors such as epitope mutations or function of accessory genes. Substitution of different primary cells as target cells will allow analysis of the susceptibility of various cell types to inhibition by CTL. Use of polyclonal CD8+ lymphocytes from infected individuals will allow evaluation of the inhibitory activity of uncloned CTL and functional comparison to CTL clones.
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