HSP72-MEDIATED AUGMENTATION OF MHC CLASS-I SURFACE EXPRESSION AND ENDOGENOUS ANTIGEN PRESENTATION

Efficient recognition of tumor cells by cytolytic T lymphocytes (CTL) is often dependent on the presentation of cytosolic peptides in the co ntext of MHC class I molecules. This process may be influenced by vari ous molecular chaperones. To analyze this influence, we have utilized B16 melanoma cells, which are not effectively recognized by MHC class I-restricted CTL. This resistance to CTL is apparently due to a very l ow level of surface MHC expression. We have found that stably transfec ted clones of B16 which constitutively express the human heat shock pr otein 72 (Hsp72) exhibit significantly increased levels of MHC class I antigens on their surface. This Hsp72-mediated up-regulation of surfa ce MHC class I antigen represents an increase in the amount of functio nal WHC-peptide complexes as measured by conformation-dependent antibo dies and recognition by MHC class I-restricted CTL. Expression of Hsp7 2 did not improve the antigen presentation defect in cells lacking the activity of the transporter associated with antigen presentation (TAP ). Moreover, mice immunized with Hsp72-expressing B16 cells, but not w ith control-transfected B16 cells, display significantly increased res istance to a subsequent challenge with live, wild-type B16. Together, our data demonstrate that the immune recognition of tumor cells can be substantially enhanced by the suitable expression of a molecular chap erone.