Targeted deletion of T-cell clones using alpha-emitting suicide MHC tetramers.
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.
Yuan
Rui Rong
RR
Molecular Pharmacology and Chemistry Program, Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
Wong
Phillip
P
McDevitt
Michael R
MR
Doubrovina
Ekaterina
E
Leiner
Ingrid
I
Bornmann
William
W
O'reilly
Richard
R
Pamer
Eric G
EG
Scheinberg
David A
DA
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
D015395:Histocompatibility Antigens Class I; D010455:Peptides