Amino-terminal extended peptide single-chain trimers are potent synthetic agonists for memory human CD8+ T cells.

Amino-terminal extended peptide single-chain trimers are potent synthetic agonists for memory human CD8+ T cells.
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DOI:
10.4049/jimmunol.1103647
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发表时间:
2012-06-15
期刊:
Journal of immunology (Baltimore, Md. : 1950)
影响因子:
--
通讯作者:
Linette GP
Linette GP
中科院分区:
其他
文献类型:
--
作者:
Carreno BM;Becker-Hapak M;Chan M;Lie WR;Wang X;Hansen TH;Linette GP

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Upon antigen exposure, most memory T cells undergo re-stimulation induced cell death. Here we describe a novel synthetic agonist, an amino-terminal extended decamer peptide expressed as a single chain trimer, the AT-SCT, that preferentially promotes the growth of memory human CD8+ T cells with minimal re-stimulation-induced cell death. Using the CMV pp65 and melanoma gp100 antigens, we observe the in vitro numerical expansion of a clonally diverse poly-functional population of antigen-specific CD8+ T cells from normal individuals and vaccinated melanoma patients, respectively. Memory CD8+ T cells stimulated with AT-SCT presented on MHC class I/II null cells show reduced cytokine production, slower kinetics of TCR down-regulation and decreased cell death when compared to native nonamer SCT-activated T cells. However, both ERK phosphorylation and cell cycle kinetics are identical in AT-SCT- and SCT-activated T cells. Probing of SCT and AT-SCT peptide-MHC (p-MHC) complexes using fluorochrome-conjugated TCR multimers suggest that nonamer and decamer-linked peptides may be anchored differently to HLA-A2 peptide binding groove. Our findings demonstrate that modified p-MHC structures such as AT-SCT can be engineered as T cell agonists to promote the growth and expansion of memory human CD8+ T cells.
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