An endogenously synthesized decamer peptide efficiently primes cytotoxic T cells specific for the HIV-1 envelope glycoprotein.
The immunodominant H-2Dd-restricted cytotoxic T lymphocyte (CTL) response to the HIV-1 gp160 envelope glycoprotein maps to a single determinant in the V3 loop, designated p18. Using a series of peptides synthesized on pins we have determined that the minimal core sequence of this determinant required for CTL recognition comprises 8 amino acids (residues 320-327). However, 9mer and 10mer peptides containing this core sequence were more effective than the 8mer peptide at sensitizing Dd-expressing target cells. To analyze the antigenicity of endogenously synthesized p18, minigenes encoding a 10-amino acid determinant (residues 318-327) and a 67-amino acid peptide (residues 281-348; containing the V3 loop) were expressed using vaccinia virus (Vac) recombinants. Both peptides were as effective as wild-type gp160 in their ability to sensitize target cells for lysis by gp160-specific CTL. Immunization of BALB/c mice with Vac recombinants encoding both gp160 peptides elicited gp160-specific CTL. These data demonstrate that both the V3 loop itself and a 10-residue epitope are sufficient to prime CTL in vivo and strongly support the potential use of minigene-encoded CTL epitopes for recombinant vaccines designed to induce protective T cell-mediated immunity against HIV-1.
Bergmann
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C
Department of Neurology, University of Southern California School of Medicine, Los Angeles 90033.
Stohlmann
S A
SA
McMillan
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M
D016915:AIDS Vaccines / Q000302:isolation & purification; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D004279:DNA, Viral / Q000235:genetics; D000939:Epitopes / Q000235:genetics; D015686:Gene Products, env / Q000235:genetics / Q000276:immunology*; D006183:H-2 Antigens; D019302:HIV Envelope Protein gp160; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000138:chemical synthesis / Q000235:genetics / Q000276:immunology*; D011498:Protein Precursors / Q000235:genetics / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D016915:AIDS Vaccines; D004279:DNA, Viral; D000939:Epitopes; D015686:Gene Products, env; D006183:H-2 Antigens; D019302:HIV Envelope Protein gp160; D009842:Oligopeptides; D011498:Protein Precursors