Identification of T-cell epitopes without B-cell activity in the first and second conserved regions of the HIV Env protein.
We have previously hypothesized that an effective vaccine against HIV should elicit cell-mediated immunity without antiviral antibody production. As a first step towards this goal we have identified potential T-cell epitopes, without B-cell activity against the native protein, from the first and second conserved sequences, and from three functionally important regions of the HIV-1 envelope protein gp160. For this approach, short peptide sequences selected by established computer programs were synthesized and chemically modified to generate either polymers with disulfide bonds, or micelles with two palmitic acid residues attached to the amino-terminal lysine. In both configurations several peptides were immunogenic without the need for coupling to carrier molecules. Of the 19 peptides we tested in our present studies, seven induced good T-cell proliferative response in mice representing four major histocompatibility complex haplotypes. None of these seven peptides produced antibodies that could recognize the envelope protein gp160.
Sastry
K J
KJ
Department of Molecular Pathology, University of Texas M.D. Anderson Cancer Centre, Houston 77030.
Arlinghaus
R B
RB
D000595:Amino Acid Sequence; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D004220:Disulfides; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000276:immunology*; D005260:Female; D015686:Gene Products, env / Q000276:immunology*; D015488:HIV Antigens / Q000276:immunology*; D019302:HIV Envelope Protein gp160; D015497:HIV-1 / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D019308:Palmitic Acid; D010169:Palmitic Acids / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology*; D011498:Protein Precursors / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D004220:Disulfides; D000939:Epitopes; D015686:Gene Products, env; D015488:HIV Antigens; D019302:HIV Envelope Protein gp160; D010169:Palmitic Acids; D010446:Peptide Fragments; D011498:Protein Precursors; D019308:Palmitic Acid