T cells integrate local and global cues to discriminate between structurally similar antigens Journal Article

   

Authors:	Voisinne, G.; Nixon, B. G.; Melbinger, A.; Gasteiger, G.; Vergassola, M.; Altan-Bonnet, G.
Article Title:	T cells integrate local and global cues to discriminate between structurally similar antigens
Abstract:	T lymphocytes' ability to discriminate between structurally related antigens has been attributed to the unique signaling properties of the Tcell receptor. However, recent studies have suggested that the output of this discrimination process is conditioned by environmental cues. Here, we demonstrate how the IL-2 cytokine, collectively generated by strongly activated Tcell clones, can induce weaker Tcell clones to proliferate. We identify the PI3K pathway as being critical for integrating the antigen and cytokine responses and for controlling cell-cycle entry. We build a hybrid stochastic/deterministic computational model that accounts for such signal synergism and demonstrates quantitatively how Tcells tune their cell-cycle entry according to environmental cytokine cues. Our findings indicate that antigen discrimination by Tcells is not solely an intrinsic cellular property but rather a product of integration of multiple cues, including local cues such as antigen quality and quantity, to global ones like the extracellular concentration of inflammatory cytokines. © 2015 The Authors.
Keywords:	signal transduction; controlled study; nonhuman; cd8+ t lymphocyte; lymphocyte proliferation; t lymphocyte; animal cell; mouse; interleukin 2; animal experiment; enzyme activation; phosphatidylinositol 3 kinase; t lymphocyte receptor; regulatory t lymphocyte; quantitative analysis; lymphocyte clone; cell density; t lymphocyte activation; immunological parameters; cytokine response; priority journal; article; antigen discrimination
Journal Title:	Cell Reports
Volume:	11
Issue:	8
ISSN:	2211-1247
Publisher:	Cell Press
Date Published:	2015-05-26
Start Page:	1208
End Page:	1219
Language:	English
DOI:	10.1016/j.celrep.2015.04.051
PROVIDER:	scopus
PUBMED:	26004178
PMCID:	PMC4516668
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-84929952162&partnerID=40&md5=cd1546ae8a5a036f56a1b777b8226d8e
Notes:	Export Date: 2 July 2015 -- Source: Scopus

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