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Improbability of harmful autoimmune responses resulting from immunization with HIV-1 envelope glycoproteins.




 

AIDS Res Hum Retroviruses. 1993 Dec;9(12):1195-208. Unique Identifier :

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 between gp120/gp160 and several human host proteins, including MHC antigens and immunoglobulins, has been perceived as the basis for immunological cross-reactivity. Binding of antibodies from sera of HIV-1-infected individuals to selected host proteins and/or to synthetic peptides derived from them and the inhibitory activity of such sera in assays measuring the functional activity of T cells provided apparent support for the autoimmunity hypothesis, which is also relevant to the issue of safety of anti-HIV-1 vaccines. Considering the possibility that the detected autoantibodies may arise for reasons other than antibody responses to gp120/gp160, the immunological cross-reactivity between gp120/gp160 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-reactivity of anti-gp120 with CD4 was undetectable (< 10(-5)%). The cross-reactivity of anti-gp120/gp160 with HLA-I and HLA-II antigens was also undetectable (< 4 x 10(-4)%) and that with other human proteins reported to have partial sequence homology with gp120/gp41 was < or = 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 harmful autoimmune responses.

Amino Acid Sequence Animal Antigens, CD4/IMMUNOLOGY *Autoimmunity Cross Reactions Gene Products, env/GENETICS/*IMMUNOLOGY Human HIV Antibodies HIV Envelope Protein gp120/GENETICS/IMMUNOLOGY HIV Envelope Protein gp41/GENETICS/IMMUNOLOGY HIV Infections/ETIOLOGY/IMMUNOLOGY HIV-1/GENETICS/*IMMUNOLOGY HLA Antigens/IMMUNOLOGY Immunization Lymphocyte Transformation Molecular Sequence Data Protein Precursors/GENETICS/IMMUNOLOGY Rabbits Sequence Homology, Amino Acid Support, U.S. Gov't, P.H.S. T-Lymphocytes/IMMUNOLOGY JOURNAL ARTICLE



 




Information in this article was accurate in July 30, 1994. The state of the art may have changed since the publication date. This material is designed to support, not replace, the relationship that exists between you and your doctor. Always discuss treatment options with a doctor who specializes in treating HIV.