The T Cell Receptor and AIDS Pathogenesis

An idiotypic network model of AIDS pathogenesis is described in which the T cell receptor plays a role both in infection and as a target of autoimmunity. This is an extension of a previously published autoimmunity model, and provides explanations for several otherwise puzzling aspects of AIDS pathogenesis. In the model HIV–specific T cells are preferentially infected, and HIV, acting as an antigen, stimulates the expansion of the infectable pool of T cells. The HIV variants that are most strongly selected are those that are recognized by the most helper T cells. HIV and suppressor T cells are subject to the same selective environment, and consequently undergo a process of convergent selection to resemble each other more and more with time. Eventually immunity against HIV cross–reacts with suppressor T cell idiotypes, disrupting the normal regulation of helper T cells. Autoimmunity ensues. The model leads to novel vaccine and therapy approaches involving the targeting and elimination of HIV–specific T cells.