The heat shock protein Hsp70 enhances antigen-specific proliferation of human CD4+ memory T cells

Heat shock proteins (HSP) can interact with a wide variety of peptides and the resulting HSP:peptide complexes are known to be highly immunogenic. The ability of HSP:peptide complexes to elicit CD8(+) T cell responses by cross-presentation of exogenous antigen via MHC class I is well known. In contrast, their role in the activation of CD4(+) T cells is less clearly defined, although several recent studies in mice and T cell lines suggest an involvement of HSP in the presentation of antigenic peptides via MHC class II. In this study we have investigated the potential of antigenic peptides from tetanus toxin and influenza hemagglutinin complexed to the human stress-inducible Hsp70 to enhance activation and proliferation of human memory CD4(+) T cells. Hsp70:peptide complexes were found to amplify the proliferation of antigen-specific CD4(+) T cells as confirmed by HLA-DR tetramer staining. Complex formation of the antigenic peptide with Hsp70 was absolutely required to elicit an antigen-specific amplification. This effect was most pronounced at low doses of antigen and decreasing APC/CD4(+) T cell ratios. Taken together, we show the potential of Hsp70 to enhance antigen-specific CD4(+) T cell proliferation and to increase the immunogenicity of presented peptides in human CD4(+) T cells.