title: Generation of CD8+ T cells specific for transporter associated with antigen processing deficient cells.
abstract: Cells with impaired transporter associated with antigen processing (TAP) function express low levels of cell surface major histocompatibility complex (MHC) class I molecules, and are generally resistant to lysis by MHC class I restricted cytotoxic T lymphocytes (CTLs). Here we report the generation of MHC class I restricted CD8(+) CTLs that surprisingly require target cell TAP deficiency for efficient recognition. C57BL/6 (B6) mice immunized with syngenic B7-1 (CD80) expressing TAP-deficient cells generated a potent CTL response against both TAP-deficient RMA-S tumor cells and TAP-deficient Con A blasts, whereas the corresponding TAP-expressing target cells were considerably less susceptible or resistant to lysis. The CTL epitopes recognized were expressed also by the human TAP-deficient cell line T2, transfected with appropriate MHC class I molecules. B6 mice immunized with B7-1-transfected TAP-deficient RMA-S cells were protected from outgrowth of a subsequent RMA-S tumor challenge. These findings are discussed in relation to the biochemical nature of MHC class I dependent CTL epitopes associated with impaired TAP function, as well as implications for immunotherapy and autoimmunity.
authors.affiliation: Microbiology and Tumor Biology Center, Karolinska Institute, Box 280, S-171 77 Stockholm, Sweden. Elisabeth.Wolpert@mtc.ki.se
authors.forename: E Z
authors.initials: EZ
authors.lastname: Wolpert
authors.forename: M
authors.initials: M
authors.lastname: Petersson
authors.forename: B J
authors.initials: BJ
authors.lastname: Chambers
authors.forename: J K
authors.initials: JK
authors.lastname: Sandberg
authors.forename: R
authors.initials: R
authors.lastname: Kiessling
authors.forename: H G
authors.initials: HG
authors.lastname: Ljunggren
authors.forename: K
authors.initials: K
authors.lastname: Kärre
mesh_terms: D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000502:physiology*; D000818:Animals; D018122:B7-1 Antigen / Q000096:biosynthesis / Q000502:physiology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D015395:Histocompatibility Antigens Class I / Q000502:physiology*; D006801:Humans; D007942:Leukemia, Experimental; D008285:Major Histocompatibility Complex; D012515:Mast-Cell Sarcoma / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D018345:Mice, Knockout; D011994:Recombinant Proteins / Q000096:biosynthesis; D013154:Spleen / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014162:Transfection; D014407:Tumor Cells, Cultured; D001613:beta 2-Microglobulin / Q000172:deficiency / Q000502:physiology
chemical_list: D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters; D018122:B7-1 Antigen; D015395:Histocompatibility Antigens Class I; D011994:Recombinant Proteins; C073119:TAP1 protein, human; C486171:Tap1 protein, mouse; D001613:beta 2-Microglobulin