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Clinical features of Kawasaki disease (KD) display overlap with common pediatric viral illnesses, leading some to hypothesize that a viral infection is the inciting event for KD. To investigate viral infection history in KD patients, we performed comprehensive serological profiling using a high-throughput phage immunoprecipitation sequencing assay covering the complete reference protein sequences of known viruses with human tropism. KD and matched febrile control sera did not demonstrate differences in antiviral antibody profiles. We conclude that in the acute and subacute phases of disease, KD patients do not exhibit serologic evidence of exposure to known viruses that differs from controls.

Theft and devastation of railway infrastructure are one of the most important factors that affect the safety of the railway transport system. In Poland, the railway transported 245.1 million passengers and 243.6 million tons of cargo in 2021, so it is extremely important to ensure the maximum possible safety standards. Theft and devastation of railway infrastructure contribute to significant material damage to railway network managers. The costs of rebuilding railway equipment are estimated at millions of zlotys every year. They also influence the proper functioning of railway traffic. Due to this phenomenon, there are delays of passenger and freight trains, the total of which amounted to over 100,000 minutes in 2021. Therefore, the effects of such hooligan acts also affect passengers and commercial customers of the railways. The article is an attempt to describe the impact of theft and devastation of railway infrastructure on its safety and the operation of railway lines in Poland. By analyzing the available statistical data and using the CSM method, as well as applying certain simplifications, it was possible to determine the approximate level of risk using techniques used in practice. Based on the adopted risk reference levels, a systematic reduction in both the probability of occurrence of negative phenomena and their consequences was observed. [ABSTRACT FROM AUTHOR]

Interactions between T cell receptors (TCRs) and their cognate tumour antigens are central to antitumour immune responses1–3; however, the relationship between phenotypic characteristics and TCR properties is not well elucidated. Here we show, by linking the antigenic specificity of TCRs and the cellular phenotype of melanoma-infiltrating lymphocytes at single-cell resolution, that tumour specificity shapes the expression state of intratumoural CD8+ T cells. Non-tumour-reactive T cells were enriched for viral specificities and exhibited a non-exhausted memory phenotype, whereas melanoma-reactive lymphocytes predominantly displayed an exhausted state that encompassed diverse levels of differentiation but rarely acquired memory properties. These exhausted phenotypes were observed both among clonotypes specific for public overexpressed melanoma antigens (shared across different tumours) or personal neoantigens (specific for each tumour). The recognition of such tumour antigens was provided by TCRs with avidities inversely related to the abundance of cognate targets in melanoma cells and proportional to the binding affinity of peptide–human leukocyte antigen (HLA) complexes. The persistence of TCR clonotypes in peripheral blood was negatively affected by the level of intratumoural exhaustion, and increased in patients with a poor response to immune checkpoint blockade, consistent with chronic stimulation mediated by residual tumour antigens. By revealing how the quality and quantity of tumour antigens drive the features of T cell responses within the tumour microenvironment, we gain insights into the properties of the anti-melanoma TCR repertoire.The authors use single-cell profiling and T cell receptor specificity screening to show how tumour antigen recognition shapes the phenotypes of CD8+ T cells and antitumour immune responses. [ABSTRACT FROM AUTHOR]

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At this time, pretransplant viral screening of donors and recipients is based on serological status and limited to certain viruses. After transplantation, patient follow-up is based on a monitoring strategy using ELISA or PCR. Such approaches exclude other emerging viruses that can affect the transplant outcome. Recently, a multiplex unbiased array, VirScan, was developed. This tool allows the detection of antibodies against viruses, using a synthetic human virome, with minimal serum and cost. We decided to test the value of VirScan in the follow-up of a cohort of transplant recipients. We enrolled 45 kidney transplant recipients and performed virus serological profiling at day 0 and day +365, using VirScan. We compared the results obtained with ELISA/PCR assays. We detected antibody responses to 39 of the 206 species of virus present in the VirScan library, with an average of 12 species of virus per sample. VirScan gave similar results to PCR/ELISA screening tests. Using VirScan, we found that anti-viral antibody responses were largely conserved in patients during the first year after transplantation, regardless of immunosuppressive treatment. Our study suggests VirScan offers an unprecedented opportunity to screen and monitor posttransplant virus infection in a cost-effective, easy, and unbiased manner. [ABSTRACT FROM AUTHOR]

Antigen discovery technologies have largely focused on major histocompatibility complex (MHC) class I-restricted human T cell receptors (TCRs), leaving methods for MHC class II-restricted and mouse TCR reactivities relatively undeveloped. Here we present TCR mapping of antigenic peptides (TCR-MAP), an antigen discovery method that uses a synthetic TCR-stimulated circuit in immortalized T cells to activate sortase-mediated tagging of engineered antigen-presenting cells (APCs) expressing processed peptides on MHCs. Live, tagged APCs can be directly purified for deconvolution by sequencing, enabling TCRs with unknown specificity to be queried against barcoded peptide libraries in a pooled screening context. TCR-MAP accurately captures self-reactivities or viral reactivities with high throughput and sensitivity for both MHC class I-restricted and class II-restricted TCRs. We elucidate problematic cross-reactivities of clinical TCRs targeting the cancer/testis melanoma-associated antigen A3 and discover targets of myocarditis-inciting autoreactive T cells in mice. TCR-MAP has the potential to accelerate T cell antigen discovery efforts in the context of cancer, infectious disease and autoimmunity., (© 2024. The Author(s).)

Developing effective strategies to prevent or treat coronavirus disease 2019 (COVID-19) requires understanding the natural immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We used an unbiased, genome-wide screening technology to determine the precise peptide sequences in SARS-CoV-2 that are recognized by the memory CD8 + T cells of COVID-19 patients. In total, we identified 3-8 epitopes for each of the 6 most prevalent human leukocyte antigen (HLA) types. These epitopes were broadly shared across patients and located in regions of the virus that are not subject to mutational variation. Notably, only 3 of the 29 shared epitopes were located in the spike protein, whereas most epitopes were located in ORF1ab or the nucleocapsid protein. We also found that CD8 + T cells generally do not cross-react with epitopes in the four seasonal coronaviruses that cause the common cold. Overall, these findings can inform development of next-generation vaccines that better recapitulate natural CD8 + T cell immunity to SARS-CoV-2., Competing Interests: Declaration of Interests A.P.F., Y.W., D.M.V.N., A.W., G.S.D., Q.X., N.N., C.R.P., A.W.C., H.J.W., A.V., K.J.O., S.A.B., and G.M. are employees of TScan Therapeutics. T.K. is a founder of TScan Therapeutics, and T.K. and G.M. hold equity in TScan Therapeutics. S.C. is a consultant for TScan Therapeutics. A patent application relating to the T-Scan technology used in the current manuscript was filed previously by The Brigham and Women’s Hospital, Inc. Provisional patent applications covering SARS-CoV-2 epitope sequences and TCR sequences described in the current manuscript as well as related uses, diagnostics, therapeutics, and vaccines for COVID-19 were filed by TScan Therapeutics, Inc., (Copyright © 2020 Elsevier Inc. All rights reserved.)