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Isolation of human MHC class II‐restricted T cell receptors from the autologous T ‐cell repertoire with potent anti‐leukaemic reactivity
Author(s) -
Weigand Luise U,
Liang Xiaoling,
Schmied Sabine,
Mall Sabine,
Klar Richard,
Stötzer Oliver J,
Salat Christoph,
Götze Katharina,
Mautner Josef,
Peschel Christian,
Krackhardt Angela M
Publication year - 2012
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/imm.12000
Subject(s) - t cell receptor , antigen , biology , adoptive cell transfer , cytotoxic t cell , t cell , major histocompatibility complex , human leukocyte antigen , immunology , streptamer , microbiology and biotechnology , in vitro , immune system , genetics
Summary Adoptive transfer of T cells genetically modified with tumour‐specific T ‐cell receptors ( TCR ) is a promising novel approach in the treatment of cancer. We have previously isolated an allorestricted MHC class I‐restricted TCR with specificity for F ormin‐like protein 1 ( FMNL 1) with potent activity against chronic lymphocytic leukaemia cells. CD 4 + T cells have been described to be highly important for tumour elimination although TCR derived from CD 4 + T cells with anti‐tumour reactivity have been only rarely described. In this study we aimed to isolate MHC class‐II‐restricted CD 4 + T cells and TCR with specificity for leukaemia antigens. We used professional antigen‐presenting cells pulsed with the leukaemia‐associated and tumour‐associated antigen FMNL 1 for stimulation of autologous T cells in vitro . We isolated two CD 4 + HLA ‐ DR ‐restricted T ‐cell clones and T ‐cell‐derived TCR with so far unknown specificity but high reactivity against lymphoma cells and native malignant cells derived from HLA ‐matched patients with diverse leukaemias. Moreover, characterization of the TCR after TCR gene transfer revealed that specific characteristics of isolated TCR as reactivity in response to T oll‐like receptors were transferable on effector cells. Our results have a major impact on the development of novel immunotherapies. They demonstrate that TCR with potent HLA ‐ DR ‐restricted anti‐leukaemic reactivity against so far undefined self‐restricted antigens can be isolated from the healthy autorestricted CD 4 + T ‐cell repertoire and these TCR are highly interesting candidate tools for novel immunotherapies.