Autoreactivity in HIV-1 infection: the role of molecular mimicry.
Autoimmunity during HIV-1 infection may contribute to the immunopathogenesis of AIDS. Titers of autoantibodies to HLA molecules and other surface markers of CD4+ T cells appear to increase with the progression of disease and may correlate with lymphopenia. Other autoantibodies are directed at a number of regulatory molecules of the immune system. Genesis of autoreactivity may be related to structural homologies of HIV-1 env-products to such functional molecules involved in the control of self-tolerance. The most impressive similarities include the HLA-DR4 and DR2, the variable regions of TCR alpha-, beta-, and gamma-chain, the Fas protein, and several functional domains of IgG and IgA. Thus, HIV-1 infection may induce dysregulation leading to autoimmune response, through a number of molecular mimicry mechanisms. Pathogenicity of antibodies to T cells could also include the activation of membrane-to-nucleus signal transducers resulting in increased apoptosis. The evolution of autoimmune mechanisms during HIV-1 infection cannot exclude, however, progression to immunoproliferative malignancy, since aspects of oligoclonal immune response to HIV-1 components may occur in several autoimmune diseases which in some instances evolve to lymphoma.
Silvestris
F
F
Department of Biomedical Sciences and Human Oncology, University of Bari, Italy.
Williams
R C
RC
Dammacco
F
F
D000595:Amino Acid Sequence; D001323:Autoantibodies / Q000096:biosynthesis; D001324:Autoantigens / Q000276:immunology; D015551:Autoimmunity; D001402:B-Lymphocytes / Q000276:immunology; D003429:Cross Reactions; D015686:Gene Products, env / Q000276:immunology; D015683:Gene Products, gag / Q000276:immunology; D015699:HIV Envelope Protein gp120 / Q000276:immunology; D015658:HIV Infections / Q000276:immunology*; D006681:HLA-D Antigens / Q000276:immunology; D006801:Humans; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D017411:Ribonucleoproteins, Small Nuclear; D012859:Sjogren's Syndrome / Q000276:immunology; D055517:snRNP Core Proteins
D001323:Autoantibodies; D001324:Autoantigens; D015686:Gene Products, env; D015683:Gene Products, gag; D015699:HIV Envelope Protein gp120; D006681:HLA-D Antigens; D017411:Ribonucleoproteins, Small Nuclear; D055517:snRNP Core Proteins