Enhanced susceptibility to cytotoxic T lymphocytes without increase of MHCclass I antigen expression after conditional overexpression of heat shock protein 70 in target cells

Antigenic peptides have been found associated with heat shock proteins (HSP ) including cytoplasmic HSP70 and heat shock cognate protein 70 as well as the endoplasmic reticulum-resident glucose-regulated protein 94. Recently, HSP70 transfection has been reported to increase MHC class I cell surface e xpression and antigen presentation on mouse melanoma B16 cells (Wells et al ., Int. Immunol. 1998. 10: 609). To analyze the effect of HSP70 on MHC clas s I cell surface expression and lysability of target cells we transfected a human melanoma cell line with the rat Hsp70-1 gene using the Tet-On system for conditional overexpression of HSP70. Induction of HSP70 did not increa se cell surface expression of HLA class I molecules in general or individua l HLA-A and B antigens in particular. Nonetheless, induction of HSP70 enhan ced susceptibility of these cells to lysis by allospecific CTL. The same ef fect was observed using an HLA-A2-restricted tyrosinase-specific CTL clone after pulsing the tyrosinase-negative target cells with the specific peptid e. Thus, HSP70 induction can increase killing by CTL without affecting MHC class I cell surface expression or antigen processing. This effect of HSP70 appears to be different from the commonly found protection exerted by HSP7 0 against stress like heat shock, and might be mediated by improving CTL-in duced apoptosis.