Article
Immunology
Maurits Damoiseaux, Jan Damoiseaux, Ingrid Pico-Knijnenburg, Mirjam van der Burg, Robbert Bredius, Gijs van Well
Summary: The patient presented with SCID-like symptoms and genetic analysis revealed a novel RFXANK mutation causing BLS type II, leading to delayed diagnosis due to lack of MHCII expression awareness.
CLINICAL IMMUNOLOGY
(2022)
Article
Genetics & Heredity
Shan Chen, Yuqing Xu, Yeqing Qian, Zhaohui Li, Minyue Dong
Summary: This study identified a genetic mutation associated with severe immunodeficiency and demonstrated its pathogenicity through experimental validation. This research has important implications for genetic counseling, prenatal diagnosis, and preimplantation genetic testing for immunodeficiency.
FRONTIERS IN GENETICS
(2022)
Article
Immunology
Hilal Uensal, Canan Caka, Hacer Neslihan Bildik, Saliha Esenboga, Alphan Kupesiz, Baris Kuskonmaz, Duygu Uckan Cetinkaya, Mirjam van Der Burg, Ilhan Tezcan, Deniz Cagdas
Summary: The study investigated the demographic, clinical, laboratory, follow-up, and treatment characteristics of 21 patients with Major Histocompatibility Complex Class II (MHC-II) deficiency. It was found that patients with Bare Lymphocyte Syndrome (BLS) exhibited clinical findings similar to severe combined immunodeficiency (SCID), and the flow cytometric MHC-II expression study played a crucial role in the diagnosis, differential diagnosis, early hematopoietic stem cell transplantation (HSCT), and post-HSCT follow-up.
SCANDINAVIAN JOURNAL OF IMMUNOLOGY
(2024)
Article
Multidisciplinary Sciences
Binkai Chi, Muhammet M. Oeztuerk, Christina L. Paraggio, Claudia E. Leonard, Maria E. Sanita, Mahtab Dastpak, Jeremy D. O'Connell, Jordan A. Coady, Jiuchun Zhang, Steven P. Gygi, Rodrigo Lopez-Gonzalez, Shanye Yin, Robin Reed
Summary: Mutations in RNA/DNA-binding proteins can cause ALS, but the exact disease mechanisms are still unclear. This study found that a group of ALS-associated proteins can affect the expression of genes involved in the MHC II antigen presentation pathway. Additionally, hematopoietic progenitor cells with mutations also exhibit disrupted MHC II expression. These findings suggest that the loss of the MHC II pathway may result in the immune system's failure to protect motor neurons from ALS-related damage.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Biochemistry & Molecular Biology
M. Cortazar-Chinarro, A. Richter-Boix, P. Rodin-Morch, P. Halvarsson, J. B. Logue, A. Laurila, J. Hoglund
Summary: Microbiomes play a crucial role in determining the ecology and behavior of their hosts. This study investigated the effects of geography, evolutionary history, and host genetics on the skin microbiome diversity and structure in a widespread amphibian. The results showed that microbiome diversity was correlated with host genetic diversity, and the bacterial community composition varied between geographical clusters and specific host genetic variations.
Article
Immunology
Fabrizio Celesti, Andrea Gatta, Mariam Shallak, Anna Maria Chiaravalli, Michele Cerati, Fausto Sessa, Roberto S. Accolla, Greta Forlani
Summary: In an animal experimental system, vaccination with glioblastoma GL261 cells expressing CIITA showed successful protection against glioblastoma growth. The activation of MHC class II through CIITA led to rapid infiltration of CD4+ and CD8+ T cells, resulting in the rejection or retardation of tumor growth. This approach demonstrates the potential application of novel immunotherapeutic strategies in the clinical setting.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Multidisciplinary Sciences
Yusuke Kasuga, Ryota Ouda, Masashi Watanabe, Xin Sun, Miki Kimura, Shigetsugu Hatakeyama, Koichi S. Kobayashi
Summary: Major histocompatibility complex (MHC) class I and II molecules are critical for adaptive immunity. The protein FBXO11 has been identified as an E3 ligase that regulates CIITA protein level through ubiquitination-mediated degradation, thus determining the level of MHC-II.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Multidisciplinary Sciences
Xuefei Zhang, Hye Suk Yoon, Aimee M. Chapdelaine-Williams, Nia Kyritsis, Frederick W. Alt
Summary: This study reveals the critical role of 3' IgH CBEs in regulating gene transcription and joining during CSR processes, especially in focusing transcriptional activities on upstream C-H locus targets.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Cell Biology
Fei Sun, Terrence Sun, Michael Kronenberg, Xianglong Tan, Chengyang Huang, Michael F. Carey
Summary: The degradation of TAF12 and MED4 in murine embryonic stem cells revealed their different roles in P-E communication, with neither directly controlling P-E looping. Degradation of TAF12 led to a significant decrease in gene expression, while degradation of MED4 consistently led to a twofold loss in gene expression.
GENES & DEVELOPMENT
(2021)
Article
Immunology
Yanan Wu, Nianzhi Zhang, Keiichiro Hashimoto, Chun Xia, Johannes M. Dijkstra
Summary: The structures of peptide-loaded major histocompatibility complex class I (pMHC-I) and class II (pMHC-II) complexes are similar, but there are differences in the components. Comparative analysis of primitive vertebrate species' pMHC-I and pMHC-II structures sheds light on the evolution of MHC structures. The establishment of pMHC-I involved the development of important new functions that have been well conserved since their early inception.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Jorge Alfonso Leon Machado, Viktor Steimle
Summary: CIITA is the master regulator of MHC class II gene expression, functioning as a non-DNA-binding activator through interactions with the MHC enhanceosome complex. In addition to its role in MHC-II gene regulation, CIITA also plays important roles in cancer, viral restriction, and inhibition of virus replication.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Letter
Oncology
Tamara Steinfass, Juliane Poelchen, Qian Sun, Giovanni Mastrogiulio, Daniel Novak, Marlene Vierthaler, Sandra Pardo, Aniello Federico, Laura Hueser, Thomas Hielscher, Rafael Carretero, Rienk Offringa, Peter Altevogt, Viktor Umansky, Jochen Utikal
Summary: Melanoma is a deadly form of skin cancer with increasing incidence. Understanding the underlying mechanisms of resistance to treatment can enhance therapy efficacy and success.
EXPERIMENTAL HEMATOLOGY & ONCOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Chrissie E. B. Ong, Yuanyuan Cheng, Hannah V. Siddle, A. Bruce Lyons, Gregory M. Woods, Andrew S. Flies
Summary: MHC-I and MHC-II molecules play critical roles in antigen presentation and T cell immunity. Two transmissible devil facial tumours (DFT1 and DFT2) exploit the MHC-I pathway to overcome immune and allogeneic barriers. This study reveals that overexpression of NLRC5 regulates the MHC-I pathway and raises interest in the expression of MHC-II in tumor cells. This finding has important implications for immunotherapy and cancer vaccine research.
Article
Immunology
Richel J. C. Bilderbeek, Maksim V. Baranov, Geert van den Bogaart, Frans Bianchi
Summary: This study reveals the over-presentation of membrane protein fragments in cytolytic and helper T cell responses. It also demonstrates the evolutionary conservation and lower frequency of mutations in transmembrane helices, suggesting that T cells are more tuned to respond to membrane proteins to avoid evasion by pathogens.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Cell Biology
Martin Plasil, Jan Oppelt, Marie Klumplerova, Jana Bubenikova, Leona Vychodilova, Eva Janova, Karla Stejskalova, Jan Futas, Ales Knoll, Agnes Leblond, Andrei D. Mihalca, Petr Horin
Summary: The major histocompatibility complex (MHC) includes class I and II genes that are vital for immune response against pathogens. These genes exhibit high levels of single nucleotide polymorphisms (SNPs) in exons encoding antigen binding sites. This study aimed to investigate the variability of MHC genes, particularly MHC class I physical haplotypes. Using long-range next-generation sequencing, alleles in exon 2 and exon 3 were identified in three genetically distinct horse breeds. A total of 116 allelic variants were found in the MHC class I genes, with 112 being novel. Extensive variability in the MHC region was confirmed, and diversifying and purifying selection were detected in the analyzed MHC class I and II loci.
Article
Immunology
Wesley Huisman, Ilse Gille, Lieve E. van der Maarel, Lois Hageman, Laura T. Morton, Rob C. M. de Jong, Mirjam H. M. Heemskerk, Derk Amsen, J. H. Frederik Falkenburg, Inge Jedema
Summary: In this study, we isolated the first functional HLA-A*01:01-restricted EBV-LMP2-specific T-cell populations and TCRs and demonstrated that these T-cell populations and T cells modified to express the LMP2-specific T-cell receptor showed IFN-gamma secretion and cytotoxicity toward EBV-LMP2-expressing malignant cell lines.
JOURNAL OF INFECTIOUS DISEASES
(2022)
Article
Biotechnology & Applied Microbiology
Miranda H. Meeuwsen, Anne K. Wouters, Lorenz Jahn, Renate S. Hagedoorn, Michel G. D. Kester, Dennis F. G. Remst, Laura T. Morton, Dirk M. van der Steen, Christiaan Kweekel, Arnoud H. de Ru, Marieke Griffioen, Peter A. van Veelen, J. H. Frederik Falkenburg, Mirjam H. M. Heemskerk
Summary: CAR T cell therapy shows potential for the treatment of B cell malignancies, but antigen-negative escape variants limit its efficacy. This study identifies promising TCRs targeting multiple antigens for the treatment of B cell malignancies through a systematic approach.
Letter
Oncology
Karima Amaador, Anne Martens, Renate de Boer, Joanne Rietveld, Mirjam Heemskerk, Caroline E. Rutten, Eric Eldering, Marie-Jose Kersten, Arnon Kater, Josephine Vos, Sanne Tonino
LEUKEMIA & LYMPHOMA
(2022)
Article
Immunology
Anna H. E. Roukens, Cilia R. Pothast, Marion Koenig, Wesley Huisman, Tim Dalebout, Tamar Tak, Shohreh Azimi, Yvonne Kruize, Renate S. Hagedoorn, Mihaela Zlei, Frank J. T. Staal, Fenna J. de Bie, Jacques J. M. van Dongen, Sesmu M. Arbous, Jaimie L. H. Zhang, Maaike Verheij, Corine Prins, Anne M. van der Does, Pieter S. Hiemstra, Jutte J. C. de Vries, Jacqueline J. Janse, Meta Roestenberg, Sebenzile K. Myeni, Marjolein Kikkert, Maria Yazdanbakhsh, Mirjam H. M. Heemskerk, Hermelijn H. Smits, Simon P. Jochems
Summary: Systemic immune cell dynamics during COVID-19 have been well-documented, but less is known about immune cells in the respiratory tract. This study characterized nasal and systemic immune cells in COVID-19 patients, showing increased inflammatory cells in the nasal mucosa during acute infection. After recovery, nasal immune cells mostly normalized, but SARS-CoV-2-specific CD8(+) T cells could persist for at least 2 months.
Article
Oncology
Tassilo L. A. Wachsmann, Anne K. Wouters, Dennis F. G. Remst, Renate S. Hagedoorn, Miranda H. Meeuwsen, Eline van Diest, Jeanette Leusen, Jurgen Kuball, J. H. Frederik Falkenburg, Mirjam H. M. Heemskerk
Summary: This study compared the activity of CAR T cells and engineered TCR T cells in targeting CD20 antigen, and found that CAR T cells were more potent in the short term but their expansion was impaired with increased antigen exposure, while eTCR T cells performed better under high antigenic pressure.
Article
Hematology
Sabine Haggenburg, Birgit Lissenberg-Witte, Rob S. van Binnendijk, Gerco den Hartog, Michel S. Bhoekhan, Nienke J. E. Haverkate, Dennis M. de Rooij, Johan van Meerloo, Jacqueline Cloos, Neeltje A. Kootstra, Dorine Wouters, Suzanne S. Weijers, Ester M. M. van Leeuwen, Hetty J. Bontkes, Saida Tonouh-Aajoud, Mirjam H. M. Heemskerk, Rogier W. Sanders, Elianne Roelandse-Koop, Quincy Hofsink, Kazimierz Groen, Lucia Cetinel, Louis Schellekens, Yvonne M. den Hartog, Belle Toussaint, Iris M. J. Kant, Thecla Graas, Emma de Pater, Willem A. Dik, Marije D. Engel, Cheyenne R. N. Pierie, Suzanne R. Janssen, Edith van Dijkman, Meliawati Poniman, Judith A. Burger, Joey H. Bouhuijs, Gaby Smits, Nynke Y. Rots, Sonja Zweegman, Arnon P. Kater, Tom van Meerten, Pim G. N. J. Mutsaers, Jaap A. van Doesum, Annoek E. C. Broers, Marit J. van Gils, Abraham Goorhuis, Caroline E. Rutten, Mette D. Hazenberg, Inger S. Nijhof
Summary: Vaccination guidelines for hematological patients are typically conservative. However, this study shows that most patients, even those with compromised immune systems, can develop sufficient antibody concentrations after receiving the Moderna vaccine. However, certain treatments may affect the vaccine's efficacy.
Article
Oncology
Rosa A. van Amerongen, Renate S. Hagedoorn, Dennis F. G. Remst, Danique C. Assendelft, Dirk M. van der Steen, Anne K. Wouters, Marian van de Meent, Michel G. D. Kester, Arnoud H. de Ru, Marieke Griffioen, Peter A. van Veelen, J. H. Frederik Falkenburg, Mirjam H. M. Heemskerk
Summary: In this study, high-avidity WT1-specific T cells were identified from the allogeneic T-cell repertoire of healthy donors. These T cells showed potent and specific anti-WT1 activity against newly identified WT1 peptides derived from primary leukemia and ovarian carcinoma samples. Additionally, T-cell clones with T-cell receptor (TCR) gene transfer showed antitumor reactivity against WT1-expressing solid tumor cell lines, acute myeloid leukemia (AML) blasts, and ovarian carcinoma patient samples. These findings suggest that these TCRs and naturally expressed WT1 peptides have potential for TCR gene transfer strategies in patients with WT1-expressing tumors, including AML and ovarian carcinoma.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Oncology
Sabine Haggenburg, Quincy Hofsink, Birgit I. Lissenberg-Witte, Annoek E. C. Broers, Jaap A. van Doesum, Rob S. van Binnendijk, Gerco den Hartog, Michel S. Bhoekhan, Nienke J. E. Haverkate, Judith A. Burger, Joey H. Bouhuijs, Gaby P. Smits, Dorine Wouters, Ester M. M. van Leeuwen, Hetty J. Bontkes, Neeltje A. Kootstra, Sonja Zweegman, Arnon P. Kater, Mirjam H. M. Heemskerk, Kaz Groen, Tom van Meerten, Pim G. N. J. Mutsaers, Tim Beaumont, Marit J. van Gils, Abraham Goorhuis, Caroline E. Rutten, Mette D. Hazenberg, Inger S. Nijhof
Summary: This study aimed to assess the effectiveness of a third mRNA-1273 vaccination in immunocompromised patients with hematologic cancers. The results showed that a third vaccination had a significant effect in patients with recovering immune systems, but yielded poorer results in certain specific patient groups. Therefore, the administration of a third dose of vaccine should be considered in patients with hematologic cancers and evaluated on an individual basis.
Article
Cell Biology
Mihaela Zlei, Igor A. Sidorov, Simone A. Joosten, Mirjam H. M. Heemskerk, Sebenzile K. Myeni, Cilia R. Pothast, Caroline S. de Brouwer, A. Linda Boomaars-van der Zanden, Krista E. van Meijgaarden, Shessy T. Morales, Els Wessels, Jacqueline J. Janse, Jelle J. Goeman, Christa M. Cobbaert, Aloys C. M. Kroes, Suzanne C. Cannegieter, Meta Roestenberg, Leonardus G. Visser, Marjolein Kikkert, Mariet C. W. Feltkamp, Sesmu M. Arbous, Frank J. T. Staal, Tom H. M. Ottenhoff, Jacques J. M. van Dongen, Anna H. E. Roukens, Jutte J. C. de Vries
Summary: This study highlights the importance of immune responses in determining disease severity and viral clearance after SARS-CoV-2 infection. Delayed viral clearance is associated with more severe disease, higher levels of neutralising antibodies, and ongoing immune activation. Early viral clearance and less critical illness are correlated with peak neutralising antibodies, higher levels of CD4 T cells, and particularly naive CD4+ T cells, suggesting their role in early control of the virus.
Letter
Hematology
Cilia R. Pothast, Kayleigh van Dijk, Emma S. Pool, Constantijn J. M. Halkes, Mirjam H. M. Heemskerk, Jennifer M. -L. Tjon
AMERICAN JOURNAL OF HEMATOLOGY
(2023)
Article
Oncology
Jessie S. Kroonen, Ilona J. de Graaf, Sumit Kumar, Dennis F. G. Remst, Anne K. Wouters, Mirjam H. M. Heemskerk, Alfred C. O. Vertegaal
Summary: Combination therapies using SUMO inhibition and DNA hypomethylation can effectively reduce cell proliferation in MYC-driven hematopoietic malignancies. In vivo experiments also showed promising results in reducing tumor growth with the combined treatment. Tailored combination therapies based on molecular mechanisms have the potential to improve cancer treatment efficacy.
Article
Biochemistry & Molecular Biology
Jesper van Eck van der Sluijs, Diede van Ens, Jolanda Brummelman, Daan Heister, Aastha Sareen, Lisa Truijen, Dorette S. van Ingen Schenau, Mirjam H. M. Heemskerk, Marieke Griffioen, Michel G. D. Kester, Nicolaas P. M. Schaap, Joop H. Jansen, Anniek B. van der Waart, Harry Dolstra, Willemijn Hobo
Summary: Non-DCs have been found to enhance the activation and expansion of antigen-specific CD8+ T cells mediated by DCs, without impairing the NK cell responses in vitro and in vivo. This provides a rationale for further clinical translation of the CD34+-derived DC-complete vaccine in hemato-oncology patients post alloSCT.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2023)
Article
Cell Biology
Ilse Gille, Renate S. Hagedoorn, Ellen M. W. van der Meer-Prins, Mirjam H. M. Heemskerk, Sebastiaan Heidt
Summary: HLA-sensitized patients on the transplant waiting list may face difficulties in finding a compatible donor organ due to antibodies and memory B cells directed against allogeneic HLA molecules. In this study, a new immunotherapy approach called Chimeric HLA Antibody Receptor (CHAR) was developed to specifically target HLA-directed humoral immune responses. The CHAR T cells showed activation and killing of HLA-specific B cells, providing evidence for their potential use in desensitizing highly sensitized solid organ transplant candidates and treating antibody-mediated rejection after transplantation.
Letter
Hematology
Tassilo L. A. Wachsmann, Miranda H. Meeuwsen, Dennis F. G. Remst, Karen Buchner, Anne K. Wouters, Renate S. Hagedoorn, J. H. Frederik Falkenburg, Mirjam H. M. Heemskerk
Meeting Abstract
Cell Biology
Ilse Gille, Renate S. Hagedoorn, Manon Vergunst, Mirjam H. M. Heemskerk, Sebastiaan Heidt
