Reversible HLA multimers (Streptamers) for the isolation of human cytotoxic T lymphocytes functionally active against tumor- and virus-derived antigens

J Immunol Methods. 2007 Mar 30;320(1-2):119-31. doi: 10.1016/j.jim.2007.01.001. Epub 2007 Jan 31.


The development of MHC/peptide multimers has facilitated the visualization and purification of antigen-specific T cells. However, the persistence of multimers leads to prolonged T cell receptor signaling and subsequently to altered T-cell function. We have recently developed a new type of MHC/peptide multimers, which can be dissociated from the T cell. Herein, we have generated and tested for the first time reversible HLA/peptide multimers, termed Streptamers, for the isolation of human T cells. The Streptamer technique demonstrates the specificity and sensitivity of conventional HLA/peptide tetramers with regards to the sorting of human T lymphocytes. This is shown for T cells directed against immunogenic peptides derived from viral and tumor-associated antigens. We show that antigen-specific cytotoxic T cells remain functionally active following Streptamer dissociation, whereas lytic function and proliferation of the T cells is impaired in the presence of conventional tetramers. These novel HLA/peptide Streptamer reagents allow the isolation of antigen-specific T cells with preserved function and, therefore, facilitate the development of adoptive T cell transfer regimens for the treatment of patients with cancer or infectious diseases.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Neoplasm / immunology*
  • Antigens, Viral / immunology*
  • Cells, Cultured
  • Cytomegalovirus / immunology
  • HLA Antigens / chemistry
  • HLA Antigens / immunology
  • HLA Antigens / isolation & purification*
  • Humans
  • MART-1 Antigen
  • Neoplasm Proteins / immunology
  • T-Lymphocytes, Cytotoxic / immunology*
  • T-Lymphocytes, Cytotoxic / physiology


  • Antigens, Neoplasm
  • Antigens, Viral
  • HLA Antigens
  • MART-1 Antigen
  • MLANA protein, human
  • Neoplasm Proteins