Shared antigenic epitopes on the V3 loop of HIV-1 gp120 and proteins on activated human T cells.
Proliferation of HIV-1 in the infected host is characterized by a progressive loss of CD4+ T lymphocytes and consequent dysregulation of the immune system. Both direct and indirect mechanisms have been proposed. We show here that proteins with molecular weights 35, 48, and 110 kDa on stimulated primary human T cells are recognized by neutralizing antibodies against the V3 loop of HIV-1 gp120. Recognition is specific since it can be blocked by a recombinant HIV-1 gp120. Furthermore, these V3 monoclonal antibodies, as well as sera from AIDS patients that recognized these V3-like proteins, induced killing of HIV-1-infected as well as uninfected T cells. This killing was also inhibited by HIV-1 gp120 V3 peptides. These results indicate that the V3 loop shares epitopes with proteins on stimulated T cells. This may be an additional autoimmune mechanism contributing to CD4+ T cell disappearance in AIDS. V3 antibodies have been proposed as potential prophylactic agents. However, if such vaccines were based on certain epitopes, they might induce cross-reacting immune responses with cellular proteins. Vaccine candidates should be evaluated for such potential effects.
Trujillo
J R
JR
Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
Rogers
R A
RA
Brain
J D
JD
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D003165:Complement System Proteins; D003429:Cross Reactions; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D000939:Epitopes / Q000032:analysis*; D018984:Epitopes, T-Lymphocyte / Q000032:analysis*; D006168:Guinea Pigs; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120 / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007106:Immune Sera; D008213:Lymphocyte Activation; D018716:Molecular Mimicry / Q000276:immunology; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000939:Epitopes; D018984:Epitopes, T-Lymphocyte; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; C059762:HIV envelope protein gp120 (305-321); D007106:Immune Sera; D010446:Peptide Fragments; D003165:Complement System Proteins