Unknown

Dataset Information

0

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 T cell 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 T cell clones, can induce weaker T cell 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 T cells tune their cell-cycle entry according to environmental cytokine cues. Our findings indicate that antigen discrimination by T cells 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.

SUBMITTER: Voisinne G 

PROVIDER: S-EPMC4516668 | biostudies-literature | 2015 May

REPOSITORIES: biostudies-literature

altmetric image

Publications

T Cells Integrate Local and Global Cues to Discriminate between Structurally Similar Antigens.

Voisinne Guillaume G   Nixon Briana G BG   Melbinger Anna A   Gasteiger Georg G   Vergassola Massimo M   Altan-Bonnet Grégoire G  

Cell reports 20150501 8


T lymphocytes’ ability to discriminate between structurally related antigens has been attributed to the unique signaling properties of the T cell 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 T cell clones, can induce weaker T cell clones to proliferate. We identify the PI3K pathway as being critical for integrating the a  ...[more]

Similar Datasets

| S-EPMC2859123 | biostudies-literature
| S-EPMC7178056 | biostudies-literature
2012-06-16 | GSE28967 | GEO
| S-EPMC6274635 | biostudies-literature
| S-EPMC3396591 | biostudies-literature
2012-06-15 | E-GEOD-28967 | biostudies-arrayexpress
| S-EPMC4404363 | biostudies-literature
| S-EPMC4858763 | biostudies-literature
| S-EPMC1634770 | biostudies-literature
| S-EPMC4970318 | biostudies-literature