Article
Oncology
Haocai Chang, Zhengzhi Zou, Jie Li, Qi Shen, Lei Liu, Xiaorui An, Sihua Yang, Da Xing
Summary: Low fluence laser therapy enhances antigen-specific immune response by upregulating MHC class II in macrophages and dendritic cells, via the activation of mitochondrial ROS signaling pathway. This treatment strategy suppresses tumor growth by altering the adaptive immune response.
Review
Immunology
Laura Santambrogio
Summary: Advances in the analysis of the MHC class II ligandome have increased our understanding of the factors that regulate the range and selection of presented peptides, and the landscape is highly sensitive to changes in protein composition.
FRONTIERS IN IMMUNOLOGY
(2022)
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
Pharmacology & Pharmacy
Carley Tasker, Jenny Patel, Vibha Jawa, Jad Maamary
Summary: A novel cell-based assay has been proposed for investigating the endosomal processing and MHC class II presentation capabilities of antigens, utilizing competition between epitopes for MHC class II binding and labeled soluble T cell receptors as detectors for epitope presentation.
Article
Biochemistry & Molecular Biology
Agnes Ulfig, Verian Bader, Marharyta Varatnitskaya, Natalie Lupilov, Konstanze F. Winklhofer, Lars Leichert
Summary: Studies have shown that N-chlorinated HSA can significantly impair the ability of macrophages to present antigens to T cells via MHC class II proteins at multiple stages, potentially preventing antigen processing by immune cells at the initial stage of infection and leading to chronic infection and inflammation.
Article
Immunology
Maria Kalomoiri, Chandana Rao Prakash, Sonja Lagstroem, Kai Hauschulz, Ewoud Ewing, Klementy Shchetynsky, Lara Kular, Maria Needhamsen, Maja Jagodic
Summary: The Human Leukocyte Antigen (HLA) locus is associated with various complex diseases, especially autoimmune and inflammatory conditions. The HLA-DR15 haplotype, for example, is a major risk factor for developing Multiple Sclerosis in Caucasians, suggesting its important role in the etiology of this chronic inflammatory disease. Recent studies indicate that the levels of HLA molecule expression, which are epigenetically controlled, also contribute to disease development.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Immunology
Nyerhovwo Obarorakpor, Deep Patel, Reni Boyarov, Nansalmaa Amarsaikhan, Joseph Ray Cepeda, Doreen Eastes, Sylvia Robertson, Travis Johnson, Kai Yang, Qizhi Tang, Li Zhang
Summary: In spontaneous type 1 diabetes (T1D) non-obese diabetic (NOD) mice, the insulin B chain peptide 9-23 (B:9-23) can bind to the MHC class II molecule (IA(g7)) in register 3 (R3), creating a bimolecular IA(g7)/InsulinB:9-23 register 3 conformational epitope (InsB:R3). InsB:R3-specific chimeric antigen receptor (CAR) can guide CAR-expressing CD8 T cells to migrate to the islets and pancreatic lymph nodes. Regulatory T cells (Tregs) specific for an islet antigen can suppress autoimmune reactivity in islets and protect against T1D.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Biochemistry & Molecular Biology
M. L. M. Jongsma, J. Neefjes, R. M. Spaapen
Summary: MHC-I molecules present a blueprint of the intracellular proteome to T cells for immune response, but pathogens and tumor cells can downmodulate MHC-I mediated antigen presentation to evade immune surveillance. While the fundamental rules of antigen presentation are well understood, new modules of regulation in this system continue to be uncovered.
MOLECULAR IMMUNOLOGY
(2021)
Review
Immunology
Karolina D. Witt
Summary: MHC class I antigen processing is a less recognized area in nonviral host-pathogen interactions, involving immunology and cell biology. This review focuses on the MHC-I antigen processing pathway and alternative sources of antigens, particularly in the context of Mycobacterium tuberculosis (Mtb) as an intracellular pathogen. It explores how Mtb manipulates host immunity for survival and proposes directions for MHC-I-focused approaches in developing vaccines against tuberculosis.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2023)
Article
Oncology
Ila J. Datar, Sacha C. Hauc, Shruti Desai, Nicole Gianino, Brian Henick, Yuting Liu, Kostas Syrigos, David L. Rimm, Paula Kavathas, Soldano Ferrone, Kurt A. Schalper
Summary: This study analyzed the distribution, immune contexture, and clinical significance of HLA class-I and -II subunits in NSCLC. The results revealed frequent and differential defects in HLA protein subunit expression in NSCLCs, associated with distinct tumor microenvironment composition and patient survival.
CLINICAL CANCER RESEARCH
(2021)
Review
Chemistry, Applied
Sabina Koj, Czeslaw Lugowski, Tomasz Niedziela
Summary: Microbial polysaccharides undergo depolymerization within antigen-presenting cells through reactive nitrogen and reactive oxygen species, without significant structural alterations. The chemical mechanisms of in-cell processes vary depending on the structural features of the complex polymers. The endosomal processing of glycoconjugates can modify their structure, affecting T-cell activation and immunogenicity. This review highlights the importance of understanding carbohydrate structural features and the current knowledge of in-cell processing of glycoconjugates.
CARBOHYDRATE POLYMERS
(2023)
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
Evolutionary Biology
Gemma Palomar, Katarzyna Dudek, Ben Wielstra, Elizabeth L. Jockusch, Michal Vinkler, Jan W. Arntzen, Gentile F. Ficetola, Masatoshi Matsunami, Bruce Waldman, Martin Tesicky, Piotr Zielinski, Wieslaw Babik
Summary: The study found that in urodele amphibians, some APGs are closely linked to MHC I genes, and all APGs show signs of episodic positive selection. However, the detected gene duplications, putative gene losses, and divergent allelic lineages suggest that if there is coevolution between APGs and MHC I, it may be more complex than originally hypothesized.
GENOME BIOLOGY AND EVOLUTION
(2021)
Article
Multidisciplinary Sciences
Jeff D. Colbert, Freidrich M. Cruz, Christina E. Baer, Kenneth L. Rock
Summary: This study reveals a molecular association between Tspan5 and MHC I molecules that is critical for the formation of MHC I nanoclusters and optimal T cell responses to antigens.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Multidisciplinary Sciences
Haiyin Liu, Kayla R. Wilson, Ashley M. Firth, Christophe Macri, Patrick Schriek, Annabelle B. Blum, Javiera Villar, Samuel Wormald, Mitch Shambrook, Bangyan Xu, Hui Jing Lim, Hamish E. G. McWilliam, Andrew F. Hill, Laura E. Edgington-Mitchell, Irina Caminschi, Mireille H. Lahoud, Elodie Segura, Marco J. Herold, Jose A. Villadangos, Justine D. Mintern
Summary: This study reveals the critical role of ubiquitin-like protein 3 (UBL3) in the trafficking process controlled by MARCH1. UBL3 has wide-ranging immunological consequences and is essential for immune responses.
NATURE COMMUNICATIONS
(2022)
Article
Microbiology
Dustin R. Middleton, Javid Aceil, Seema Mustafa, Amy Paschall, Fikri Y. Avci
Summary: The pneumococcal serine-rich repeat protein (PsrP) is a glycosylated adhesin that plays a crucial role in the attachment of Streptococcus pneumoniae to host cells. This study characterized the glycosyltransferases responsible for PsrP glycosylation in S. pneumoniae and found that at least four glycosyltransferases are essential for biofilm formation, cell adherence, and lung infection establishment. The findings suggest that glycosylated PsrP could be a potential candidate for the design of serotype-independent pneumococcal vaccines.
JOURNAL OF BACTERIOLOGY
(2021)
Article
Immunology
Jiachen Huang, Aaron D. Gingerich, Fredejah Royer, Amy Paschall, Alma Pena-Briseno, Fikri Y. Avci, Jarrod J. Mousa
Summary: Despite the widespread use of vaccines, Streptococcus pneumoniae remains a leading cause of bacterial pneumonia. Vaccines are effective against most serotypes, but rise in nonvaccine serotypes and moderate efficacy against some vaccine serotypes contribute to high disease incidence. Human monoclonal antibodies targeting conserved pneumococcal proteins show potential for disease prevention and treatment, with opsonophagocytic activity suggesting a mechanism of protection.
INFECTION AND IMMUNITY
(2021)
Article
Microbiology
Ahmet Ozdilek, Jiachen Huang, Rachelle Babb, Amy Paschall, Dustin R. Middleton, Jeremy A. Duke, Liise-Anne Pirofski, Jarrod J. Mousa, Fikri Y. Avci
Summary: Capsular polysaccharides (CPSs) are major virulence factors on the surfaces of many human bacterial pathogens. The predominant use of antibodies expressing VH3 gene family in interactions with CPSs has been observed in humans and mice, with critical amino acids in carbohydrate binding identified through mutational analysis. This study provides insights into the structural requirements for interactions between CPSs and antibodies, with implications for knowledge-based vaccine design.
Article
Biochemistry & Molecular Biology
Jeremy A. Duke, Amy Paschall, John Glushka, Andrew Lees, Kelley W. Moremen, Fikri Y. Avci
Summary: This study explores the use of galactose oxidase (GOase) in a chemoenzymatic approach to generate a conjugate vaccine against Streptococcus pneumoniae. The results show that GOase can generate aldehyde motifs on the capsular polysaccharides of S. pneumoniae in a site-specific and reversible manner. The conjugate vaccine synthesized using GOase demonstrates improved humoral response and functional protection compared to the traditional sodium periodate oxidation method.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Immunology
Amy Paschall, Ahmet Ozdilek, Sydney L. Briner, Melinda A. Brindley, Fikri Y. Avci
Summary: The COVID-19 pandemic emphasized the need for improved vaccination strategies and therapeutic responses. This study found that immunosuppressive drugs used in autoimmune disorders can impact immune responses to SARS-CoV-2 spike protein vaccination, and temporarily suspending certain immunosuppressants may enhance antibody responses.
Article
Chemistry, Medicinal
Jeremy A. Duke, Amy Paschall, Lloyd S. Robinson, Cory J. Knoot, Evgeny Vinogradov, Nichollas E. Scott, Mario F. Feldman, Fikri Y. Avci, Christian M. Harding
Summary: This study presents a novel bioconjugation platform for producing a prototype multivalent GBS conjugate vaccine that shows promise in eliciting functional antibodies against GBS capsule. This proof-of-concept research marks the first step towards developing a next-generation multivalent GBS bioconjugate vaccine.
ACS INFECTIOUS DISEASES
(2021)
Article
Biochemistry & Molecular Biology
Ahmet Ozdilek, Fikri Y. Avci
Summary: It is crucial to generate vaccine antigens that are immunologically similar to native antigens. This review explores the potential impact of host protein glycosylation on the immune responses generated by nucleic acid vaccines against bacterial and viral pathogens.
CURRENT OPINION IN STRUCTURAL BIOLOGY
(2022)
Article
Immunology
Javid Aceil, Amy Paschall, Cory J. Knoot, Lloyd S. Robinson, Nichollas E. Scott, Mario F. Feldman, Christian M. Harding, Fikri Y. Avci
Summary: Capsular polysaccharides are widely used as the main components of glycoconjugate vaccines against bacterial diseases. Pneumococcal conjugate vaccines are administered globally to prevent pneumococcal disease. Our previous research has shown the efficacy of a bioconjugation method in producing pneumococcal conjugate vaccines.
Article
Microbiology
Javid Aceil, Aarya Venkat, Eric Pan, Natarajan Kannan, Fikri Y. Avci
Summary: Despite the use of multivalent conjugate vaccines, pneumococcal pneumonia is still a high-priority disease according to WHO. A protein-based, serotype-independent vaccine targeting the pneumococcal serine-rich repeat protein (PsrP) has the potential to provide comprehensive coverage. A study using genomes of clinically isolated pneumococci from the Global Pneumococcal Sequencing project revealed that PsrP is present in at least 50% of all isolates, indicating its strong vaccine potential, especially in non-vaccine serotypes.
MICROBIOLOGY SPECTRUM
(2023)
Review
Immunology
Jeremy A. Duke, Fikri Y. Avci
Summary: The incidence of invasive pneumococcal disease (IPD) caused by infection with Streptococcus pneumoniae has been decreasing due to vaccination programs. However, the global burden of S. pneumoniae is still significant, emphasizing the need for new vaccination strategies. This review focuses on immune mechanisms triggered by existing pneumococcal vaccines and discusses challenges faced in selecting serotypes and using pneumococcal-derived proteins as vaccine antigens.
Review
Microbiology
Mukaddes S. Cinar, Afaq Niyas, Fikri Y. Avci
Summary: Serine-rich-repeat proteins (SRRPs) play important functional roles in bacterial-host interactions and can cause diseases. They have shared domains, including serine-rich repeat regions, and function through glycosylation reactions. Studies have shown the significance of SRRPs and their glycans in host-microbe communications.
JOURNAL OF BACTERIOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Berna Tumoglu, Aidan Keelaghan, Fikri Y. Avci
Summary: Protein-carbohydrate interactions are crucial in maintaining immune homeostasis and regulating immune processes. This review focuses on the immune interactions of macrophage galactose-type lectin (MGL) and Tn carbohydrate antigen, highlighting their role in regulating effector T cells, immune suppression, and pathogen recognition.
Meeting Abstract
Immunology
Jarrod J. Mousa, Jiachen Huang, Aaron D. Gingerich, Fredejah Royer, Amy V. Paschall, Fikri Y. Avci
JOURNAL OF IMMUNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Paeton L. Wantuch, Satya Jella, Jeremy A. Duke, Jarrod J. Mousa, Bernard Henrissat, John Glushka, Fikri Y. Avci
Summary: Paenibacillus sp. 32352 produces an enzyme, Pn3Pase, capable of degrading the capsular polysaccharide of Streptococcus pneumoniae serotype 3. Recent studies have shown the potential of Pn3Pase as a protection against highly virulent S. pneumoniae serotype 3 infections. Biochemical analysis and mutagenesis studies have revealed that Pn3Pase establishes a new CAZy GH family and identified catalytic residues and essential domains for function. This study contributes to understanding the mechanistic and structural aspects of Pn3Pase, establishing it as a potential therapeutic approach against type 3 S. pneumoniae infections.
Article
Chemistry, Multidisciplinary
Shiyi Zhou, Zipeng Zhen, Amy V. Paschall, Lijun Xue, Xueyuan Yang, Anne-Gaelle Bebin Blackwell, Zhengwei Cao, Weizhong Zhang, Mengzhe Wang, Yong Teng, Gang Zhou, Zibo Li, Fikri Y. Avci, Wei Tang, Jin Xie
Summary: This study developed a photodynamic therapy approach using nanoparticles specifically targeting FAP, which efficiently eradicated CAFs in tumors and induced anti-cancer immunity in murine models. Interestingly, the treatment not only elicited cellular immunity against cancer cells, but also stimulated an anti-CAFs immunity, as supported by adoptive cell transfer study.
ADVANCED FUNCTIONAL MATERIALS
(2021)