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

Blood. 2004 Oct 15;104(8):2397-402. doi: 10.1182/blood-2004-01-0324. Epub 2004 Jun 24.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes / cytology*
  • CD8-Positive T-Lymphocytes / immunology*
  • Cell Line
  • Clone Cells / cytology*
  • Flow Cytometry
  • Histocompatibility Antigens Class I / immunology*
  • Humans
  • Lymphocyte Count
  • Mice
  • Peptides / immunology
  • Substrate Specificity
  • Temperature

Substances

  • Histocompatibility Antigens Class I
  • Peptides