R. Schirmbeck et al., PRIMING OF CLASS I-RESTRICTED CYTOTOXIC T-LYMPHOCYTES BY VACCINATION WITH RECOMBINANT PROTEIN ANTIGENS, Vaccine, 13(9), 1995, pp. 857-865
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.