RESTORATION OF MHC CLASS-I SURFACE EXPRESSION AND ENDOGENOUS ANTIGEN PRESENTATION BY A MOLECULAR CHAPERONE

Presentation of cytosolic peptides in the context of major histocompat ibility complex (MHC) class I antigen is crucial for immune recognitio n of virus-infected and malignant cells. This process, which is often defective in cancer cells, involves a series of cellular events which may be facilitated by heat shock proteins (molecular chaperones). To a ddress the influence of chaperone function on the presentation of cyto solic peptides, we have utilized B16 melanoma cells (H-2(b)). These tu mour cells are resistant to lysis by MHC class I-restricted cytotoxic T lymphocytes (CTL), due to a very low level of surface MHC expression . The authors found that stably transfected clones of B16 expressing a heterologous heat shock protein (Hsp65) exhibit significantly increas ed levels of MHC class I antigens on their surface, and are effectivel y lysed by alloreactive CTL. These MHC class I molecules can form func tional MHC-peptide complexes which are recognized by virus-specific CT L. Moreover, mice immunized with Hsp65-expressing tumour cells, but no t with control-transfected tumour cells, display a significantly incre ased resistance to a subsequent challenge with live, wild-type B16. To gether, these results indicate that the suitable expression of a molec ular chaperone can overcome a defect in MHC class I expression and ant igen presentation, and suggest a novel approach to cancer immunotherap y.