DOWN-REGULATION OF THE EXPRESSION AND FUNCTION OF THE TRANSPORTER ASSOCIATED WITH ANTIGEN-PROCESSING IN MURINE TUMOR-CELL LINES EXPRESSING IL-10

The MHC class I molecules present antigenic peptides to CTL, The pepti des are delivered to the secretory pathway by TAP, which is formed by the association of MHC-encoded TAP1 and TAP2 gene products, Tumor cell s incubated or transfected with IL-10 had decreased but peptide-induci ble expression of MHC class I, decreased sensitivity to MHC class I-re stricted CTL, and increased NK sensitivity, We here demonstrate that I L-10 expression in the murine lymphoma RMA inhibits the TAP-dependent translocation of peptides to the endoplasmic reticulum, resulting in a ccumulation of immature MHC class I molecules in the endoplasmic retic ulum and subsequently low expression of cell surface MHC class I molec ules, This finding is explained by a down-regulation of expression of TAP1 and TAP2, observed in IL-10-transfected RMA cells as well as in I L-10-transfected P815 mastocytoma cells, In the J558L plasmacytoma cel l line, constitutively expressing high levels of IL-10, increased TAP- dependent translocation of peptides and expression of cell surface MHC class I could be induced by IL-10 antisense expression, IL-10 is the first example to demonstrate that a cytokine can decrease the expressi on and function of the TAP1/2 molecular complex and, in more general t erms, the first example of a cytokine with an inhibitory effect on MHC class I-mediated Ag presentation.