HEAT-SHOCK PROTEIN-PEPTIDE COMPLEXES, RECONSTITUTED IN-VITRO, ELICIT PEPTIDE-SPECIFIC CYTOTOXIC T-LYMPHOCYTE RESPONSE AND TUMOR-IMMUNITY

Heat shock protein (HSP) preparations derived from cancer cells and vi rus-infected cells have been shown previously to elicit cancer-specifi c or virus-specific immunity. The immunogenicity of HSP preparations h as been attributed to peptides associated with the HSPs. The studies r eported here demonstrate that immunogenic HSP-peptide complexes can al so be reconstituted in vitro. The studies show that (a) complexes of h sp70 or gp96 HSP molecules with a variety of synthetic peptides can be generated in vitro; (b) the binding of HSPs with peptides is specific in that a number of other proteins tested do not bind synthetic pepti des under the conditions in which gp96 molecules do; (c) HSP-peptide c omplexes reconstituted in vitro are immunologically active, as tested by their ability to elicit antitumor immunity and specific CD8(+) cyto lytic T lymphocyte response; and (d) synthetic peptides reconstituted in vitro with gp96 are capable of being taken up and re-presented by m acrophage in the same manner as gp96-peptides complexes generated in v ivo. These observations demonstrate that HSPs are CD8(+) T cell respon se-eliciting adjuvants.