IMPROBABILITY OF HARMFUL AUTOIMMUNE RESPONSES RESULTING FROM IMMUNIZATION WITH HIV-1 ENVELOPE GLYCOPROTEINS

Autoimmunity mediated by cross-reactive antibodies, elicited by HIV-1 envelope glycoproteins gp120/gp160, has been postulated to contribute to the pathogenesis of AIDS. Partial amino acid sequence homology betw een gp120/gp160 and several human host proteins, including MHC antigen s and immunoglobulins, has been perceived as the basis for immunologic al cross-reactivity. Binding of antibodies from sera of HIV-1-infected individuals to selected host proteins and/or to synthetic peptides de rived from them and the inhibitory activity of such sera in assays mea suring the functional activity of T cells provided apparent support fo r the autoimmunity hypothesis, which is also relevant to the issue of safety of anti-HIV-1 vaccines. Considering the possibility that the de tected autoantibodies may arise for reasons other than antibody respon ses to gp120/gp160, the immunological cross-reactivity between gp120/g p160 and the relevant host proteins was investigated using hyperimmune rabbit anti-gp120/gp160 and monoclonal antibodies. As determined from dilution end-point comparisons for polyclonal anti-gp120, the cross-r eactivity of anti-gp120 with CD4 was undetectable (<10(-5)%). The cros s-reactivity of anti-gp120/gp160 with HLA-I and HLA-II antigens was al so undetectable (<4 x 10(-4)%) and that with other human proteins repo rted to have partial sequence homology with gp120/gp41 was less-than-o r-equal-to 0.013%. Anti-gp120/gp160 did not have detectable inhibitory effects in functional assays measuring proliferative T cell responses . Therefore, immunization with gp120/gp160 is unlikely to elicit harmf ul autoimmune responses.