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The cancer‐germline antigen TRAG‐3 stimulates Th1‐type, Toll‐like receptor 8‐negative antigen‐specific CD4+ regulatory T cells
Author(s) -
Kudela Pavol,
Janjic Bratislav,
Fourcade Julien,
Kirkwood John M.,
Maillere Bernard,
Zarour Hassane M.
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1079.19
Subject(s) - antigen , epitope , biology , t cell , foxp3 , cancer research , cytotoxic t cell , cd8 , immunology , melanoma , immune system , microbiology and biotechnology , in vitro , biochemistry
TRAG‐3 is a cancer‐germline antigen expressed by tumors of different histological types including melanoma, breast, and lung cancers. We have previously demonstrated that TRAG‐3 stimulates spontaneous Th1‐type CD4+ T cell response against a single immunodominant and promiscuous MHC class II epitope in patients with stage IV melanoma. Here, we have shown that some of the TRAG‐3‐specific CD4+ T cell clones isolated from the PBLs of melanoma patients and normal donors inhibited the proliferation of allogenic naïve CD4+ T cells in response to anti‐CD3 antibody stimulation and acted in a cell‐to‐cell contact‐dependent fashion. The capability of these TRAG‐3‐specific CD4+ T cell clones to suppress IL‐2 production by responder cells was depended upon their activation by the cognate antigen. The TRAG‐3‐specific regulatory T cell clones did not express Toll‐like receptor 8 and no correlation was found between the level of Foxp3 expression and regulatory functions. Collectively, our findings demonstrate the capability of the same cancer‐germline‐derived epitope to stimulate both antigen‐specific helper and regulatory T cells and emphasize the need for novel therapeutic interventions to preferentially stimulate antigen‐specific helper T cells in vivo. This work was supported by NIH/NCI Grants CA90360 and CA112198.