Polypyrimidine tract binding protein 1 regulates the activation of mouse CD8 T cells.

The RNA-binding protein polypyrimidine tract binding protein 1 (PTBP1) has been found to have roles in CD4 T-cell activation, but its function in CD8 T cells remains untested. We show it is dispensable for the development of naïve mouse CD8 T cells, but is necessary for the optimal expansion and production of effector molecules by antigen-specific CD8 T cells in vivo. PTBP1 has an essential role in regulating the early events following activation of the naïve CD8 T cell leading to IL-2 and TNF production. It is also required to protect activated CD8 T cells from apoptosis. PTBP1 controls alternative splicing of over 400 genes in naïve CD8 T cells in addition to regulating the abundance of ∼200 mRNAs. PTBP1 is required for the nuclear accumulation of c-Fos, NFATc2, and NFATc3, but not NFATc1. This selective effect on NFAT proteins correlates with PTBP1-promoted expression of the shorter Aß1 isoform and exon 13 skipped Aß2 isoform of the catalytic A-subunit of calcineurin phosphatase. These findings reveal a crucial role for PTBP1 in regulating CD8 T-cell activation.

An integrated proteome and transcriptome of B cell maturation defines poised activation states of transitional and mature B cells.

During B cell maturation, transitional and mature B cells acquire cell-intrinsic features that determine their ability to exit quiescence and mount effective immune responses. Here we use label-free proteomics to quantify the proteome of B cell subsets from the mouse spleen and map the differential expression of environmental sensing, transcription, and translation initiation factors that define cellular identity and function. Cross-examination of the full-length transcriptome and proteome identifies mRNAs related to B cell activation and antibody secretion that are not accompanied by detection of the encoded proteins. In addition, proteomic data further suggests that the translational repressor PDCD4 restrains B cell responses, in particular those from marginal zone B cells, to a T-cell independent antigen. In summary, our molecular characterization of B cell maturation presents a valuable resource to further explore the mechanisms underpinning the specialized functions of B cell subsets, and suggest the presence of 'poised' mRNAs that enable expedited B cell responses.

The timing of differentiation and potency of CD8 effector function is set by RNA binding proteins.

CD8+ T cell differentiation into effector cells is initiated early after antigen encounter by signals from the T cell antigen receptor and costimulatory molecules. The molecular mechanisms that establish the timing and rate of differentiation however are not defined. Here we show that the RNA binding proteins (RBP) ZFP36 and ZFP36L1 limit the rate of differentiation of activated naïve CD8+ T cells and the potency of the resulting cytotoxic lymphocytes. The RBP function in an early and short temporal window to enforce dependency on costimulation via CD28 for full T cell activation and effector differentiation by directly binding mRNA of NF-κB, Irf8 and Notch1 transcription factors and cytokines, including Il2. Their absence in T cells, or the adoptive transfer of small numbers of CD8+ T cells lacking the RBP, promotes resilience to influenza A virus infection without immunopathology. These findings highlight ZFP36 and ZFP36L1 as nodes for the integration of the early T cell activation signals controlling the speed and quality of the CD8+ T cell response.

Assessment of genetic variability for grain nutrients from diverse regions: potential for wheat improvement.

BACKGROUND: A total of 150 bread wheat genotypes representing 121 Indian and 29 Turkish origin were screened for nutrient concentrations and grain protein content. Elemental and grain protein composition were studied by Inductively Coupled Plasma-Atomic Emission Spectrophotometer and LECO analyser, respectively. The study was performed to determine the variability in nutrient concentrations present in the collected wheat genetic material from two countries. RESULTS: Several fold variations among genotypes existed for almost all the elements. Three major components of principal component analysis (PCA) revealed 60.8% variation among the genotypes. Nutrient variables segregated into two groups, one group containing all the macroelements except sulphur; and another cluster containing proteins and all the microelements except Zn and Mn. Pearson correlation analysis and heat-map were in accordance with each other determining strong positive association between P-K, Mn-Zn, Mg-S and Cu-protein content. Also, PCA and hierarchical grouping divided all the Indian and Turkish genotypes in two main clusters. CONCLUSIONS: Nutritional profile differentiated the genotypes from two countries into separate groups. However, some of the varieties were closely associated and indicated the success of global wheat exchange programs. While most of the correlations were in agreement with the previous studies, non-association of zinc with grain protein content directed towards its control by some other genetic factors. Some of the experimental wheat varieties with promising nutrient content have been suggested for future wheat advancement programs. Results obtained will be supportive for breeders involved in wheat biofortification programs, food industries and people relying on whole grain wheat products.