Human heat shock protein 70 peptide complexes specifically activate antimelanoma T cells

Members of the heat shock protein 70 (HSP70) family display a broad cellula r localization and thus bind a repertoire of chaperoned peptides potentiall y derived from proteins of different cellular compartments. In this report, we show that HSP70 purified from human melanoma can activate T cells recog nizing melanoma differentiation antigens in an antigen- and HLA class I-dep endent fashion. HLA class I-restricted antimelanoma T cells were susceptibl e to MHC-restricted, HSP70-dependent stimulation, indicating that HSP70 com plexed peptides were able to gain access to the class I HLA presentation pa thway. In addition, MHC matching between the melanoma cells used as a sourc e of HSP and the responding T cells were not required, indicating that HSP7 0 activation may occur across MHC barriers. Besides the MHC-restricted and peptide-dependent activation pathway, HSP70 with no endogenous complexed pe ptides or HSP70 purified from antigen-negative cells was also able to induc e IFN-gamma release by antimelanoma T cells by a MHC-independent mechanism. In this case, however, higher doses of HSP70 were required. The capacity t o activate class I-restricted, antitumor T cells as well as antigen-present ing cells, together with the finding that the HSP70 chaperoned peptide repe rtoire includes melanoma-shared epitopes, holds promise for a HSP70-based c ancer vaccine.