Dynamic allostery in the peptide/MHC complex enables TCR neoantigen selectivity.

The inherent antigen cross-reactivity of the T cell receptor (TCR) is balanced by high specificity. Surprisingly, TCR specificity often manifests in ways not easily interpreted from static structures. Here we show that TCR discrimination between an HLA-A*03:01 (HLA-A3)-restricted public neoantigen and its wild-type (WT) counterpart emerges from distinct motions within the HLA-A3 peptide binding groove that vary with the identity of the peptide's first primary anchor.

The Evolving T Cell Receptor Recognition Code: The Rules Are More Like Guidelines.

αβ T cell receptor (TCR) recognition of peptide-MHC complexes lies at the core of adaptive immunity, balancing specificity and cross-reactivity to facilitate effective antigen discrimination. Early structural studies established basic frameworks helpful for understanding and contextualizing TCR recognition and features such as peptide specificity and MHC restriction. However, the growing TCR structural database and studies launched from structural work continue to reveal exceptions to common assumptions and simplifications derived from earlier work.

Clinical decision instruments for predicting mortality in patients with cirrhosis seeking emergency department care.

Objective: Clinical decision instruments (CDIs) could be useful to aid risk stratification and disposition of emergency department (ED) patients with cirrhosis. Our primary objective was to derive and internally validate a novel Cirrhosis Risk Instrument for Stratifying Post-Emergency department mortality (CRISPE) for the outcomes of 14- and 30-day post-ED mortality. Secondarily, we externally validated the existing Model for End-Stage Liver Disease (MELD) scores for explicit use in ED patients and prediction of the same outcomes.

Long-read sequencing of hundreds of diverse brains provides insight into the impact of structural variation on gene expression and DNA methylation.

Structural variants (SVs) drive gene expression in the human brain and are causative of many neurological conditions. However, most existing genetic studies have been based on short-read sequencing methods, which capture fewer than half of the SVs present in any one individual. Long-read sequencing (LRS) enhances our ability to detect disease-associated and functionally relevant structural variants (SVs); however, its application in large-scale genomic studies has been limited by challenges in sample preparation and high costs.