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

The Journal of Immunology : Official Journal of the American Association of Immunologists
Beatriz M CarrenoGerald P Linette

Abstract

Upon Ag exposure, most memory T cells undergo restimulation-induced cell death. In this article, we describe a novel synthetic agonist, an N-terminal extended decamer peptide expressed as a single-chain trimer, the amino-terminal extended peptide MHC class I single-chain trimer (AT-SCT), which preferentially promotes the growth of memory human CD8(+) T cells with minimal restimulation-induced cell death. Using CMV pp65 and melanoma gp100 Ags, we observe the in vitro numerical expansion of a clonally diverse polyfunctional population of Ag-specific CD8(+) T cells from healthy 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 downregulation, and decreased cell death compared with native nonamer MHC class I single-chain trimer (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 complexes using fluorochrome-conjugated TCR multimers suggests that nonamer- and decamer-linked peptides may be anchored differently to the HLA-A2 peptide-binding groove. Our findings demon...Continue Reading

References

Mar 15, 1991·Proceedings of the National Academy of Sciences of the United States of America·J H RussellP Meleedy-Rey
Jan 1, 1996·Annual Review of Immunology·J Sloan-Lancaster, P M Allen
Mar 21, 1998·The Journal of Experimental Medicine·B CombadièreM J Lenardo
May 23, 1998·Annual Review of Immunology·M M DavisY Chien
Mar 22, 2002·The Journal of Immunology : Official Journal of the American Association of Immunologists·Yik Y L YuTed H Hansen
Dec 25, 2002·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Anna K ThomasJames L Riley
May 21, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Marek CebecauerImmanuel F Luescher
Oct 21, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Lydie TrautmannMarc Bonneville
Nov 10, 2005·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Gerald P LinetteFrank G Haluska
Feb 24, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Xiaoyun ZhuHing C Wong
Mar 23, 2006·Annual Review of Immunology·Markus G RudolphIan A Wilson
Sep 20, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Hiroshi Takata, Masafumi Takiguchi
Mar 22, 2007·Molecular Therapy : the Journal of the American Society of Gene Therapy·Megan M SuhoskiCarl H June
May 31, 2007·The Journal of Experimental Medicine·Melissa L PrecopioRichard A Koup
Aug 28, 2007·Chemistry & Biology·Vesselin MitaksovDaved H Fremont
Sep 20, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Hua ZhangCrystal L Mackall
Jun 6, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Andrew D Wells
Jun 23, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Stéphanie GrasDominique Housset
Nov 6, 2009·The New England Journal of Medicine·Gemma G KenterCornelis J M Melief
May 21, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·C Siddiq Abdul-AlimCassian Yee
Jul 20, 2010·Immunological Reviews·Andrew L SnowMichael J Lenardo
Sep 14, 2010·Trends in Immunology·Ted H HansenDaved H Fremont
Aug 10, 2011·Proceedings of the National Academy of Sciences of the United States of America·Dibyendu SamantaSteven C Almo
Aug 27, 2011·Immunity·Nu Zhang, Michael J Bevan
Nov 3, 2011·Immunology·John S BridgemanDavid K Cole

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