Priming of class I-restricted cytotoxic T lymphocytes by vaccination with recombinant protein antigens.
We investigated the specific priming of MHC class I-restricted cytotoxic T lymphocytes (CTL) by different protein antigen preparations in mice. The recombinant viral protein antigens tested are of potential relevance for the design of subunit vaccines. They include the hepatitis B virus (HBV) surface antigen (S-antigen), the HIV-1 gp160 envelope protein, and a chimeric HIV-1 Pr55-gag/V3-3 retrovirus-like particle. In addition, ovalbumin (OVA) was tested. The native or denatured particulate (multimeric) or monomeric form of these protein antigens was injected by various routes into mice. Class I-restricted CTL were efficiently primed by a single low-dose injection of HBV S-antigen particles or the chimeric HIV-1 Pr55-gag/V3-3 particles. After SDS-denaturation, gel-purified monomeric S-antigen and monomeric Pr55-gag/V3-3 fusion protein were still very efficient in priming CTL. CTL sensitization was not detected in a (primary or boosted) response to even high doses of native OVA or native HIV-1 gp160. Denaturation of these two antigens by detergent strikingly increased their immunogenicity for CTL. Immunization of mice with non-treated or SDS-denatured antigenic peptides representing the relevant CTL-defined epitopes of the tested protein antigens did not prime CTL. These data indicate that native, particulate and denatured, monomeric protein antigens efficiently stimulate a class I-restricted CTL response.
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D003902:Detergents; D015686:Gene Products, env / Q000737:chemistry / Q000276:immunology*; D015683:Gene Products, gag / Q000235:genetics / Q000276:immunology; D015699:HIV Envelope Protein gp120 / Q000235:genetics / Q000276:immunology; D019302:HIV Envelope Protein gp160; D015497:HIV-1 / Q000276:immunology*; D006514:Hepatitis B Surface Antigens / Q000737:chemistry / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D010047:Ovalbumin / Q000276:immunology; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology; D011489:Protein Denaturation; D011498:Protein Precursors / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D011994:Recombinant Proteins / Q000737:chemistry / Q000276:immunology; D018411:Spodoptera; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014407:Tumor Cells, Cultured
D017931:DNA Primers; D003902:Detergents; D015686:Gene Products, env; D015683:Gene Products, gag; D015699:HIV Envelope Protein gp120; D019302:HIV Envelope Protein gp160; C059762:HIV envelope protein gp120 (305-321); D006514:Hepatitis B Surface Antigens; D015395:Histocompatibility Antigens Class I; D010446:Peptide Fragments; D011498:Protein Precursors; D011994:Recombinant Proteins; C059767:p55 gag precursor protein, Human immunodeficiency virus 1; D010047:Ovalbumin