Reversible HLA multimers (Streptamers) for the isolation of human cytotoxic T lymphocytes functionally active against tumor- and virus-derived antigens.
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.
Neudorfer
Julia
J
Department of Hematology/Oncology, Klinikum rechts der Isar, Technical University of Munich, Germany.
Schmidt
Burkhard
B
Huster
Katharina M
KM
Anderl
Florian
F
Schiemann
Matthias
M
Holzapfel
Gerd
G
Schmidt
Thomas
T
Germeroth
Lothar
L
Wagner
Hermann
H
Peschel
Christian
C
Busch
Dirk H
DH
Bernhard
Helga
H
D000951:Antigens, Neoplasm / Q000276:immunology*; D000956:Antigens, Viral / Q000276:immunology*; D002478:Cells, Cultured; D003587:Cytomegalovirus / Q000276:immunology; D006680:HLA Antigens / Q000737:chemistry / Q000276:immunology / Q000302:isolation & purification*; D006801:Humans; D058965:MART-1 Antigen; D009363:Neoplasm Proteins / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000502:physiology
D000951:Antigens, Neoplasm; D000956:Antigens, Viral; D006680:HLA Antigens; D058965:MART-1 Antigen; C548667:MLANA protein, human; D009363:Neoplasm Proteins