Inserm UMRS1131, Institut de Génétique Moléculaire, Université Paris 7, Hôpital St. Louis, F-75010 Paris, France; ICCVS, University of Gdańsk, Science, ul. Wita Stwosza 63, 80-308 Gdańsk, Poland; Department of Medical Biosciences, Building 6M, Umeå University, 901 85 Umeå, Sweden; RECAMO, Masaryk Memorial Cancer Institute, Zluty kopec 7, 65653 Brno, Czech Republic. Electronic address:
Published: April 2022
AI Article Synopsis
Article Abstract
The accumulation of protein aggregates is toxic and linked to different diseases such as neurodegenerative disorders, but the role of the immune system to target and destroy aggregate-carrying cells is still relatively unknown. Here we show a substrate-specific presentation of antigenic peptides to the direct MHC class I pathway via autophagy. We observed no difference in presentation of peptides derived from the viral EBNA1 protein following suppression of autophagy by knocking down Atg5 and Atg12. However, the same knock down treatment suppressed the presentation from ovalbumin. Fusing the aggregate-prone poly-glutamine (PolyQ) to the ovalbumin had no effect on antigen presentation via autophagy. Interestingly, fusing the EBNA1-derived gly-ala repeat (GAr) sequence to ovalbumin rendered the presentation Atg5/12 independent. We also demonstrate that the relative levels of protein expression did not affect autophagy-mediated antigen presentation. These data suggest a substrate-dependent presentation of antigenic peptides for the MHC class I pathway via autophagy and indicate that the GAr of the EBNA1 illustrates a novel virus-mediated mechanism for immune evasion of autophagy-dependent antigen presentation.
Department of Pediatrics, Children's Cancer Research Center, Kinderklinik München Schwabing, TUM School of Medicine, Technical University of Munich, Munich, Germany.
Introduction: Pediatric sarcomas, including osteosarcoma (OS), Ewing sarcoma (EwS) and rhabdomyosarcoma (RMS) carry low somatic mutational burden and low MHC-I expression, posing a challenge for T cell therapies. Our previous study showed that mediators of monocyte maturation sensitized the EwS cell line A673 to lysis by HLA-A*02:01/CHM1-specific allorestricted T cell receptor (TCR) transgenic CD8 T cells (CHM1 CD8 T cells).
Methods: In this study, we tested a panel of monocyte maturation cytokines for their ability to upregulate immunogenic cell surface markers on OS, EwS and RMS cell lines, using flow cytometry.
We present MMPred, a software tool that integrates epitope prediction and sequence alignment algorithms to streamline the computational analysis of molecular mimicry events in autoimmune diseases. Starting with two protein or peptide sets (e.g.
Department of Microbiology and Immunology and Stark Neuroscience Research Institute, Indiana University School of Medicine, Indianapolis, IN, United States.
In recent years, increasing evidence has highlighted the critical role of myeloid cells, specifically those that present antigen (APCs) in health and disease. These shape the progression and development of neurodegenerative disorders, where considerable interplay between the immune system and neurons influences the course of disease pathogenesis. Antigen-presenting myeloid cells display different classes of major histocompatibility complex (MHC) and MHC-like proteins on their surface for presenting various types of antigens to a wide variety of T cells.
Immune checkpoint inhibitors (ICIs) and their combination with other therapies such as chemotherapy, fail in most cancer patients. We previously identified the PDZ-LIM domain-containing protein 2 (PDLIM2) as a bona fide tumor suppressor that is repressed in lung cancer to drive cancer and its chemo and immunotherapy resistance, suggesting a new target for lung cancer therapy improvement. In this study, human clinical samples and data were used to investigate genetic and epigenetic changes in lung cancer.
Bromodomain and extra-terminal domain (BET) proteins, including BRD4, bind acetylated chromatin and co-activate gene transcription. A BET inhibitor, JQ1, prevents and reverses pathological cardiac remodeling in preclinical models of heart failure. However, the underlying cellular mechanisms by which JQ1 improves cardiac structure and function remain poorly defined.
