SuntmaryVaccination of mice with heat shock proteins isolated from tumor cells induces immunity to subsequent challenge with those tumor cells the heat shock protein was isolated from but not with other tumor cells (Udono, H., and P. K. Srivastava. 1994. J. Immunol. 152:5398-5403).The spedficity of this immune response is caused by tumor-derived peptides bound to the heat shock proteins (Udono., H., and P. K. . J. Exit Med. 178:1391-1396. Our experiments show that a single immunization with the heat shock protein gp96 isolated from fl-galactosidase (fl-gal) expressing P815 cells (ofDBA/2 origin) induces cytotoxic T lymphocytes (CTLs) specific for B-gal, in addition to minor H an.tigens expressed by these cells. CTLs can be induced in mice that are major histocompatibility complex (MHC) identical to the gp96 donor cells (H-2 a) as well as in mice with a different MHC (H-2b). Thus, gp96 is able to induce "cross priming" (Matzinger, P., and M. J. Bevan. 1977. Cell. Iramunol. 33:92-100), indicating that gp96-associated peptides are not limited to the MHC class I ligands of the gp96 donor cell. Our data confirm the notion that samples of all cellular antigens presentable by MHC class I molecules are represented by peptides associated with gp96 molecules of that cell, even if the fitting MHC molecule is not expressed. In addition, we extend previous reports on the in vivo immunogenicity of peptides associated gp96 molecules to two new groups of antigens, minor H antigens, and proteins expressed in the cytosol.

Minor histocompatibility (H) antigens can be peptides derived from cellular proteins that are presented on the cell surface by major histocompatibility complex (MHC) class I molecules. This is similar to viral antigens, because in both cases cytotoxic T lymphocytes (CTLs) recognize artificially produced peptides loaded on target cells. Naturally processed minor H peptides were found to be similar to those artificial CTL-epitopes, as far as size and hydrophobicity is concerned. The peptides studied were isolated from a transfectant that expressed a model CTL-defined antigen, beta-galactosidase, from male cells that express H-Y, which has been known operationally since 1955, and from cells that express H-4, known since 1961.

Our data demonstrate that capsomeres are potent inducers of CTL responses similar to completely assembled T‫7؍‬ VLPs. This result is of potential relevance for the development of (combined prophylactic and therapeutic) HPV-specific vaccines, since capsomeres can be produced easily and also can be modified to incorporate heterologous sequences such as early HPV proteins.