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Peptide‐β2‐microglobulin‐major histocompatibility complex expressing cells are potent antigen‐presenting cells that can generate specific T cells
Author(s) -
Obermann Sonja,
Petrykowska Susanne,
Manns Michael P.,
Korangy Firouzeh,
Greten Tim F.
Publication year - 2007
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/j.1365-2567.2007.02616.x
Subject(s) - cytotoxic t cell , antigen presenting cell , antigen , major histocompatibility complex , cd8 , t cell , adoptive cell transfer , biology , antigen presentation , streptamer , immunology , priming (agriculture) , interleukin 21 , microbiology and biotechnology , immune system , in vitro , biochemistry , botany , germination
Summary Adoptive T‐cell therapy represents a promising therapeutic approach for the treatment of cancer. Successful adoptive immunotherapy depends on the ex vivo priming and expansion of antigen‐specific T cells. However, the in vitro generation of adequate numbers of functional antigen‐specific T cell remains a major obstacle. It is important to develop efficient and reproducible methods to generate high numbers of antigen‐specific T cells for adoptive T‐cell transfer. We have developed a new artificial antigen‐presenting cell (aAPC) by transfection of major histocompatibility (MHC) class I negative Daudi cells with a peptide‐β2‐microglobulin–MHC fusion construct (single‐chain aAPC) ensuring presentation of the peptide–MHC complex of interest. Using this artificial antigen‐presenting cell, we could generate up to 9·2 × 10 8 antigen‐specific cytotoxic CD8 + T cells from 10 ml blood. In vitro generated T cells lysed endogenously presented antigens. Direct comparison of the single‐chain aAPC with autologous monocyte‐derived dendritic cells demonstrated that these cells were equally efficient in stimulation of T cells. Finally, we were able to generate antigen‐specific T cell lines from perpheral blood mononuclear cells of patients receiving cytotoxic chemotherapy. The use of single‐chain aAPC represent a promising option for the generation of antigen‐specific CD8 + T cells, which could be used for adoptive T‐cell therapy.