Lower frequencies of circulating suppressive regulatory T cells and higher frequencies of CD4 naïve T cells at baseline are associated with severe immune-related adverse events in immune checkpoint inhibitor-treated melanoma.

Background: Immune-related adverse events (irAEs) are major barriers of clinical management and further development of immune checkpoint inhibitors (ICIs) for cancer therapy. Therefore, biomarkers associated with the onset of severe irAEs are needed. In this study, we aimed to identify immune features detectable in peripheral blood and associated with the development of severe irAEs that required clinical intervention.

PEPMatch: a tool to identify short peptide sequence matches in large sets of proteins.

Background: Numerous tools exist for biological sequence comparisons and search. One case of particular interest for immunologists is finding matches for linear peptide T cell epitopes, typically between 8 and 15 residues in length, in a large set of protein sequences. Both to find exact matches or matches that account for residue substitutions.

Epitope-Specific T Cell Receptor Data and Tools in the Immune Epitope Database.

T cells play a critical role in the response of the immune system to non-self antigens. The Immune Epitope Database (IEDB) continuously curates published T cell data, among other immune-related data, and allows users to create custom queries based on their research interests and aims. The IEDB's companion site, the IEDB Analysis Resource, features a number of tools for analysis and prediction of immune epitopes; these include TCRMatch, a new tool used to predict candidate epitopes for T cell receptors with unknown specificity.

CD4+CCR6+ T cells dominate the BCG-induced transcriptional signature.

Background: The century-old Mycobacterium bovis Bacillus Calmette-Guerin (BCG) remains the only licensed vaccine against tuberculosis (TB). Despite this, there is still a lot to learn about the immune response induced by BCG, both in terms of phenotype and specificity.

Methods: We investigated immune responses in adult individuals pre and 8 months post BCG vaccination.

NetTCR-2.0 enables accurate prediction of TCR-peptide binding by using paired TCRα and β sequence data.

Prediction of T-cell receptor (TCR) interactions with MHC-peptide complexes remains highly challenging. This challenge is primarily due to three dominant factors: data accuracy, data scarceness, and problem complexity. Here, we showcase that "shallow" convolutional neural network (CNN) architectures are adequate to deal with the problem complexity imposed by the length variations of TCRs.

TCRMatch: Predicting T-Cell Receptor Specificity Based on Sequence Similarity to Previously Characterized Receptors.

The adaptive immune system in vertebrates has evolved to recognize non-self antigens, such as proteins expressed by infectious agents and mutated cancer cells. T cells play an important role in antigen recognition by expressing a diverse repertoire of antigen-specific receptors, which bind epitopes to mount targeted immune responses. Recent advances in high-throughput sequencing have enabled the routine generation of T-cell receptor (TCR) repertoire data.

Comparison of HLA ligand elution data and binding predictions reveals varying prediction performance for the multiple motifs recognized by HLA-DQ2.5.

Binding prediction tools are commonly used to identify peptides presented on MHC class II molecules. Recently, a wealth of data in the form of naturally eluted ligands has become available and discrepancies between ligand elution data and binding predictions have been reported. Quantitative metrics for such comparisons are currently lacking.

Deletion of Topoisomerase 1 in excitatory neurons causes genomic instability and early onset neurodegeneration.

Topoisomerase 1 (TOP1) relieves torsional stress in DNA during transcription and facilitates the expression of long (>100 kb) genes, many of which are important for neuronal functions. To evaluate how loss of Top1 affected neurons in vivo, we conditionally deleted (cKO) Top1 in postmitotic excitatory neurons in the mouse cerebral cortex and hippocampus. Top1 cKO neurons develop properly, but then show biased transcriptional downregulation of long genes, signs of DNA damage, neuroinflammation, increased poly(ADP-ribose) polymerase-1 (PARP1) activity, single-cell somatic mutations, and ultimately degeneration.

Single neuron transcriptome analysis can reveal more than cell type classification: Does it matter if every neuron is unique?

A recent single cell mRNA sequencing study by Dueck et al. compares neuronal transcriptomes to the transcriptomes of adipocytes and cardiomyocytes. Single cell omic approaches such as those used by the authors are at the leading edge of molecular and biophysical measurement.