PRIMING OF CLASS I-RESTRICTED CYTOTOXIC T-LYMPHOCYTES BY VACCINATION WITH RECOMBINANT PROTEIN ANTIGENS

We investigated the specific priming of MHC class I-restricted cytotox ic T lymphocytes (CTL) by different protein antigen preparations in mi ce. The recombinant viral protein antigens tested are of potential rel evance for the design of subunit vaccines. They include the hepatitis B virus (HBV) surface antigen (S-antigen), the HIV-1 gp160 envelope pr otein, and a chimeric HIV-1 Pr55-gag/V3-3 retrovirus-like particle. In addition, ovalbumin (OVA) was tested, The native or denatured particu late (multimeric) or monomeric form of these protein antigens was inje cted by various routes into mice. Class I-restricted CTL were efficien tly primed by a single low-dose injection of HBV S-antigen particles o r the chimeric HIV-1 Pr55-gag/V3-3 particles. After SDS-denaturation, gel-purified monomeric S-antigen and monomeric Pr55-gag/V3-3 fusion pr otein 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 b y detergent strikingly increased their immunogenicity for CTL. Immuniz ation of mice with non-treated or SDS-denatured antigenic peptides rep resenting the relevant CTL-defined epitopes of the tested protein anti gens did not prime CTL. These data indicate that native, particulate a nd denatured, monomeric protein antigens efficiently stimulate a class I-restricted CTL response.