Priming of class I-restricted cytotoxic T lymphocytes by vaccination with recombinant protein antigens.

ABSTRACT

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.