Antigen-specific downregulation of T cells by doxorubicin delivered through a recombinant MHC II-peptide chimera

Sofia Casares, Alexandru C. Stan, Constantin A. Bona, Teodor D. Brumeanu*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

22 Scopus citations


As the number of drugs with potential therapeutic use for T-cell-mediated diseases increases, there is a need to find methods of delivering such drugs to T cells. The major histocompatibility complex (MHC)-peptide complexes are the only antigen-specific ligands for the T-cell receptor (TCR) expressed on T cells, and they may be an appropriate drug delivery system. We engineered a soluble bivalent MHC class II-peptide chimera on the immunoglobulin scaffold (I-Edαβ/Fcγ2a/HA110-120, DEF) that binds stably and specifically to CD4 T cells recognizing the HA110-120 peptide. Doxorubicin, a powerful antimitogenic anthracycline, was enzymatically assembled on the galactose residues of a DEF chimera. The DEF-gal-Dox construct preserved both the binding capacity to hemagglutinin (HA)-specific T cells, and the drug toxicity. Brief exposure of HA-specific T cells to DEF-gal-Dox construct in vitro was followed by drug internalization in the lysosomes, translocation to the nucleus, and apoptosis. Administration of DEF-gal-Dox to mice expressing the TCR-HA transgene reduced the frequency of TCR-HA T cells in the spleen and thymus by 27% and 42%, and inhibited HA proliferative capacity by 40% and 60%, respectively. It has not been demonstrated previously that pharmacologically active drugs able to modulate T-cell functions can be delivered to T cells in an antigen-specific manner by soluble, bivalent MHC II-peptide chimeras.

Original languageEnglish
Pages (from-to)142-147
Number of pages6
JournalNature Biotechnology
Issue number2
StatePublished - 2001
Externally publishedYes


  • CD4 T cells
  • Doxorubicin
  • MHC class II-peptide chimera
  • T-cell downregulation


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