Finding a heat-shock absorber

Load the heat-shock protein Hsp70 with a peptide from a tumor-specific antigen, then inject it into a mouse bearing a tumor with the same antigen, and the mouse will mount a vigorous immune response that can significantly reduce tumor progression. The result is promising, but how does it work? Studying human Hsp70, Becker et al. (page 1277) now show that the cell surface protein CD40 binds specifically to peptide-loaded Hsp70, apparently mediating the uptake of the bound peptide into antigen-presenting cells.The binding of Hsp70 to CD40 occurs at the ATPase domain of Hsp70, and is strongly dependent on the presence of a peptide substrate on the heat-shock protein. This could explain why previous efforts, where Hsp70 binding was examined in the absence of nucleotides and peptide substrate, failed to identify the interaction. As the cochaperone...