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.
Hoffmann
G W
GW
Department of Microbiology and Immunology, University of British Columbia, Vancouver, Canada.
D016915:AIDS Vaccines / Q000276:immunology; D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology*; D001323:Autoantibodies / Q000276:immunology; D015551:Autoimmunity / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D015483:HIV Antibodies / Q000276:immunology; D015488:HIV Antigens / Q000276:immunology; D015497:HIV-1 / Q000254:growth & development / Q000276:immunology; D006801:Humans; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
D016915:AIDS Vaccines; D001323:Autoantibodies; D015483:HIV Antibodies; D015488:HIV Antigens; D011948:Receptors, Antigen, T-Cell