Initially, children were thought to be spared from disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, a month into the epidemic, a novel multisystem inflammatory syndrome in children (MIS-C) emerged. Herein, we report on the immune profiles of nine MIS-C cases. All MIS-C patients had evidence of prior SARS-CoV-2 exposure, mounting an antibody response with intact neutralization capability. Cytokine profiling identified elevated signatures of inflammation (IL-18 and IL-6), lymphocytic and myeloid chemotaxis and activation (CCL3, CCL4, and CDCP1) and mucosal immune dysregulation (IL-17A, CCL20, CCL28). Immunophenotyping of peripheral blood revealed reductions of non-classical monocytes, and subsets of NK- and T- lymphocytes, suggesting extravasation to affected tissues. Finally, we profiled the auto-antigen reactivity of MIS-C plasma, which revealed both known disease-associated autoantibodies (anti-La) and novel candidates that recognize endothelial, gastrointestinal and immune-cell antigens. All patients were treated with anti-IL6R antibody and/or IVIG, which led to rapid disease resolution.

What is universal about music, and what varies? We built a corpus of ethnographic text on musical behavior from a representative sample of the world’s societies, as well as a discography of audio recordings. The ethnographic corpus reveals that music (including songs with words) appears in every society observed; that music varies along three dimensions (formality, arousal, religiosity), more within societies than across them; and that music is associated with certain behavioral contexts such as infant care, healing, dance, and love. The discography—analyzed through machine summaries, amateur and expert listener ratings, and manual transcriptions—reveals that acoustic features of songs predict their primary behavioral context; that tonality is widespread, perhaps universal; that music varies in rhythmic and melodic complexity; and that elements of melodies and rhythms found worldwide follow power laws.

Predicting the binding affinity of major histocompatibility complex I (MHC I) proteins and their peptide ligands is important for vaccine design. We introduce an open-source package for MHC I binding prediction, MHCflurry. The software implements allele-specific neural networks that use a novel architecture and peptide encoding scheme. When trained on affinity measurements, MHCflurry outperformed the standard predictors NetMHC 4.0 and NetMHCpan 3.0 overall and particularly on non-9-mer peptides in a benchmark of ligands identified by mass spectrometry. The released predictor, MHCflurry 1.2.0, uses mass spectrometry datasets for model selection and showed competitive accuracy with standard tools, including the recently released NetMHCpan 4.0, on a small benchmark of affinity measurements. MHCflurry's prediction speed exceeded 7,000 predictions per second, 396 times faster than NetMHCpan 4.0. MHCflurry is freely available to use, retrain, or extend, includes Python library and command line interfaces, may be installed using package managers, and applies software development best practices.

Highlights d New pan-allele MHC class I binding predictor d Antigen processing predictor trained on mass spectrometryidentified MHC ligands d Combined model outperforms existing methods d Open source Python package with command line and library interfaces

Affinity maturation refines a naive B-cell response by selecting mutations in antibody variable domains that enhance antigen binding. We describe a B-cell lineage expressing broadly neutralizing influenza virus antibodies derived from a subject immunized with the 2007 trivalent vaccine. The lineage comprises three mature antibodies, the unmutated common ancestor, and a common intermediate. Their heavy-chain complementarity determining region inserts into the conserved receptor-binding pocket of influenza HA. We show by analysis of structures, binding kinetics and long time-scale molecular dynamics simulations that antibody evolution in this lineage has rigidified the initially flexible heavy-chain complementarity determining region by two nearly independent pathways and that this preconfiguration accounts for most of the affinity gain. The results advance our understanding of strategies for developing more broadly effective influenza vaccines.immunity | antigen recognition | X-ray crystallography E xposure to a novel antigen, whether by infection or vaccination, induces an initial naive B-cell response. Cells bearing B-cell receptors (BCRs) that bind the antigen in question, even with relatively low affinity, proliferate selectively. In the continued presence of antigen, additional proliferation, accompanied by somatic hypermutation of the rearranged Ig heavy-and light-chain genes, leads to selection of cells with BCRs (and secreted antibodies) that bind more tightly to antigen than their precursors-a process known as affinity maturation (1-3). Recent methodological advances make it possible to study the history of this process in a given subject by isolating a number of individual B cells at a suitable time point after vaccination or infection and cloning their recombined heavy-and light-chain variable regions (4-6). If a subset of the variable regions thus identified derives from the same progenitor, one can infer the clonal lineage that gave rise to the observed genes, including the unmutated common ancestor (UCA) and the other unobserved intermediates at the interior nodes of the clonal tree with tips that are the genes of the mature antibodies (Fig. 1A). Structural and biochemical changes that occur during affinity maturation can be analyzed, and the mechanism of affinity enhancement elucidated.The influenza B-cell clonal lineage shown in Fig. 1A derives from plasmablasts sorted from a sample taken from an adult subject 1 wk after administration of the 2007 trivalent inactivated influenza virus vaccine. It includes just three mature B-cell clones. We have shown that one member of this lineage (CH65) bears a heavy-chain complementary determining region 3 (CDR H3) loop that inserts into the HA receptor-binding pocket, mimics the influenza virus receptor sialic acid, and has unusual breadth of neutralizing capacity (31 of 36 H1 strains tested) (7). We have now extended the structural and functional analysis to the entire lineage. By determining the structure and binding properties of the UCA and intermediate 2...