Activation and transcriptional characterization
of mouse T cells
stimulated by IFs presenting lower affinity pMHC. (A) Flow cytometry
quantification of the percentage of activated CD25+CD69+ OT-I T cells at different time points. Statistical significance
was determined with two-way ANOVA on logit-transformed data with posthoc
Tukey’s multiple comparison test. (B) Production of IFNγ
by OT-I T cells at different time points by ELISA. Statistical significance
was determined with two-way ANOVA on log-transformed data with posthoc
Tukey’s multiple comparison test. (C) OT-I T cells were stimulated
for three days, after which the division index based on CTV dilution
(right) was quantified as a measure of proliferation. Statistical
significance was determined with one-way ANOVA on log-transformed
data with posthoc Tukey’s multiple comparison test. (D) Flow
cytometry quantification of the percentage of lysed B16-OVA melanoma
target cells 24 h after coincubation with OT-I T cells prestimulated
for 20 h. Statistical significance was determined with two-way ANOVA
on logit-transformed data with posthoc Tukey’s multiple comparison
test. (A–D) n = 3 in three independent experiments.
p-Values are indicated in the figure. (E,F) Antigen-specific OT-1
I T cells were either unstimulated (0 h), or stimulated for 8 or 22
h with SIITFEKL-loaded DCs or IF-pMHC(SIIT)/IL-2 in triplicate
in one experiment. (E) Heatmap depicting z-scores of differential
genes (Benjamini-Hochberg adjusted p-value < 0.05 and fold change
> 2-fold) compared to unstimulated cells (0 h). Gene clusters were
obtained using k-means clustering. The columns are ordered according
to treatment time point and mouse (three biological replicates per
condition). (F) Gene ontology analysis of the five gene clusters,
as depicted in (E), for which the three most enriched terms are visualized.
X-axis and colors depict −log10 of the Benjamini-Hochberg-adjusted p-values for over-representation of the most enriched gene
ontology terms in each cluster compared to expected. Higher values
indicate stronger enrichment for the specific terms. Dot size indicates
how many genes are present in the enriched gene sets. IFN: Interferon;
I.s.: immune system; IL: interleukins; PL: prolactin; GH: growth hormones;
BDNF: brain-derived neurotrophic factor; CXCR4: C-X-C Motif Chemokine
Receptor 4; Neg. regulation: negative regulation; Costim.: costimulation;
Adj.: adjusted.