The Cytotoxic T Lymphocyte Response to the Immunodeficiency Viruses

Virus-specific Cytotoxic T Lymphocytes (CTLs) recognize antigen in association with the polymorphic products of the major histocompatibility complex (MHC). The presentation results from the partial degradation of virally encoded proteins within the cytosol, most probably by the proteosome complex. The mature MHC-peptide complexes transit through the Golgi apparatus where each has three carbohydrate moieties added before they egress to the cell surface, where the complex, which consists of a viral peptide bound to a specific class I molecule, may be recognized by the T cell receptor of the CTL. The principle behind the measurement of HIV-specific CTL activity is to place CTL effector cells from infected individuals together with appropriate target cells in vitro, and to measure lysis of these target cells by the effector cells. Limiting dilution analysis is used to derive quantitative estimates of the frequencies of virus-specific CTL precursors (CTLp). This is a method by which the CTL response can be analyzed at the level of the individual responding cell. Discrepancies between limiting dilution analysis and functional or staining data suggest that many effector cells in blood may be terminally differentiated and unable to divide, perhaps comparable to the expanded population in the acute phase of HIV infection. However, it remains apparent that unusually high precursor frequencies of virus-specific CTLs are found during HIV infection. There is an increasing body of evidence to suggest that CTLs play a crucial role in the control of HIV throughout infection and may even be able to offer some degree of protection.