Targeted deletion of T-cell clones using alpha-emitting suicide MHC tetramers

Immunosuppressive agents in current use are nonspecific. The capacity to delete specific CD8T-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 Ac-225 (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. (C) 2004 by The American Society of Hematology.