GENERATION OF CD8(-CELLS SPECIFIC FOR TRANSPORTER ASSOCIATED WITH ANTIGEN-PROCESSING DEFICIENT CELLS() T)

Cells with impaired transporter associated with antigen processing (TA P) function express low levels of cell surface major histocompatibilit y complex (MHC) class I molecules, and are generally resistant to lysi s by MHC class I restricted cytotoxic T lymphocytes (CTLs). Here we re port the generation of MHC class I restricted CD8(+) CTLs that surpris ingly require target cell TAP deficiency for efficient recognition. C5 7BL/6 (B6) mice immunized with syngenic B7-1 (CD80) expressing TAP-def icient cells generated a potent CTL response against both TAP-deficien t RMA-S tumor cells and TAP-deficient Con A blasts, whereas the corres ponding TAP-expressing target cells were considerably less susceptible or resistant to lysis. The CTL epitopes recognized were expressed als o by the human TAP-deficient cell line T2, transfected with appropriat e MHC class I molecules. B6 mice immunized with B7-1-transfected TAP-d eficient RMA-S cells were protected from outgrowth of a subsequent RMA -S tumor challenge. These findings are discussed in relation to the bi ochemical nature of MHC class I dependent CTL epitopes associated with impaired TAP function, as well as implications for immunotherapy and autoimmunity.