ALLOACTIVATED CYTOTOXIC T-CELLS RECOGNIZE THE CARBOXY-TERMINAL DOMAINOF HUMAN IMMUNODEFICIENCY VIRUS-1 GP120 ENVELOPE GLYCOPROTEIN

Infection with the human immunodeficiency virus (HIV) virus leads to c linical disease in humans but not in chimpanzees. Progression to disea se is associated with activation of the immune system followed by loss of T helper cell function and a slow decline in CD4-positive lymphocy tes.The presence of autoreactive and cytotoxic cells in humans but not chimpanzees suggests that mechanisms other than, or in addition to, d irect virus-induced cell killing, are required for disease to develop. The observed changes are similar to those seen in chronic allogeneic disease. Here we show that a peptide from the carboxy terminus of gp12 0, predicted to have a structure similar to the major alpha-helices of major histocompatibility complex (MHC) class I and class II, acts as a cytolytic target when presented on syngeneic cells for alloactivated cytotoxic T effector cells. These data add further evidence to the hy pothesis that HIV can act as an allostimulant due to its dual properti es of CD4 binding and MHC mimicry. The ability to signal nonspecifical ly through the T cell receptor could explain the initially paradoxical responses of proliferation, anergy and apoptosis.