title: Targeted deletion of T-cell clones using alpha-emitting suicide MHC tetramers.
abstract: Immunosuppressive agents in current use are nonspecific. The capacity to delete specific CD8 T-cell clones of unique specificity could prove to be a powerful tool for dissecting the precise role of CD8(+) T cells in human disease and could form the basis for a safe, highly selective therapy of autoimmune disorders. Major histocompatibility complex (MHC) tetramers (multimeric complexes capable of binding to specific CD8 T-cell clones) were conjugated to (225)Ac (an alpha-emitting atomic nanogenerator, capable of single-hit killing from the cell surface) to create an agent for CD8 T-cell clonal deletion. The "suicide" tetramers specifically bound to, killed, and reduced the function of their cognate CD8 T cells (either human anti-Epstein-Barr virus (EBV) or mouse anti-Listeria in 2 model systems) while leaving the nonspecific control CD8 T-cell populations unharmed. Such an approach may allow a pathway to selective ablation of pathogenic T-cell clones ex vivo or in vivo without disturbing general immune function.
authors.affiliation: Molecular Pharmacology and Chemistry Program, Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
authors.forename: Rui Rong
authors.initials: RR
authors.lastname: Yuan
authors.forename: Phillip
authors.initials: P
authors.lastname: Wong
authors.forename: Michael R
authors.initials: MR
authors.lastname: McDevitt
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Doubrovina
authors.forename: Ingrid
authors.initials: I
authors.lastname: Leiner
authors.forename: William
authors.initials: W
authors.lastname: Bornmann
authors.forename: Richard
authors.initials: R
authors.lastname: O'reilly
authors.forename: Eric G
authors.initials: EG
authors.lastname: Pamer
authors.forename: David A
authors.initials: DA
authors.lastname: Scheinberg
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology*; D002460:Cell Line; D002999:Clone Cells / Q000166:cytology*; D005434:Flow Cytometry; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D018655:Lymphocyte Count; D051379:Mice; D010455:Peptides / Q000276:immunology; D013379:Substrate Specificity; D013696:Temperature
chemical_list: D015395:Histocompatibility Antigens Class I; D010455:Peptides