Targeted deletion of T-cell clones using alpha-emitting suicide MHC tetramers. Academic Article uri icon

Overview

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 date

  • June 24, 2004

Research

keywords

  • CD8-Positive T-Lymphocytes
  • Clone Cells
  • Histocompatibility Antigens Class I

Identity

Scopus Document Identifier

  • 4944254829

Digital Object Identifier (DOI)

  • 10.1182/blood-2004-01-0324

PubMed ID

  • 15217835

Additional Document Info

volume

  • 104

issue

  • 8