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 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.
Neurath
A R
AR
Lindsley F. Kimball Research Institute, New York Blood Center, New York 10021.
Strick
N
N
Li
Y Y
YY
Jiang
S
S
D000595:Amino Acid Sequence; D000818:Animals; D015551:Autoimmunity; D015704:CD4 Antigens / Q000276:immunology; D003429:Cross Reactions; D015686:Gene Products, env / Q000235:genetics / Q000276:immunology*; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120 / Q000235:genetics / Q000276:immunology; D019302:HIV Envelope Protein gp160; D015700:HIV Envelope Protein gp41 / Q000235:genetics / Q000276:immunology; D015658:HIV Infections / Q000209:etiology / Q000276:immunology; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D006680:HLA Antigens / Q000276:immunology; D006801:Humans; D007114:Immunization; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D011498:Protein Precursors / Q000235:genetics / Q000276:immunology; D011817:Rabbits; D017386:Sequence Homology, Amino Acid; D013601:T-Lymphocytes / Q000276:immunology
D015704:CD4 Antigens; D015686:Gene Products, env; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D019302:HIV Envelope Protein gp160; D015700:HIV Envelope Protein gp41; D006680:HLA Antigens; D011498:Protein Precursors