Inhibition of ii synthesis

Abstract

Disclosed are expressible reverse gene constructs, and oligonucleotides, which are characterized by the ability to hybridize with an Ii mRNA molecule, thereby inhibiting translation of the Ii mRNA molecule. These compositions are referred to generally as inhibitors of Ii expression. Also disclosed are MHC class II-positive antigen presenting cells containing an inhibitor of Ii expression. A particularly important class of MHC class II-positive antigen presenting cells are malignant MHC class II-positive antigen presenting cells (e.g., leukemia, lymphoma and melanoma). Also disclosed are methods which results in the display of an autodeterminant peptide, in association with an MHC class II protein, on the surface of an MHC class II-positive antigen presenting cell. In such methods, a specific inhibitor of Ii synthesis is introduced into an MHC class II-positive antigen presenting cell. The specific inhibitor functions, directly or indirectly, through the formation of a duplex molecule with mRNA encoding Ii. The formation of the duplex molecule functions to inhibit Ii synthesis at the translational level. Also disclosed are therapeutic methods for the treatment of malignancy in an MHC class II-positive antigen presenting cell, and autodeterminant peptides which are isolated from an MHC class II-positive antigen presenting cell.