Article
Immunology
Yaritza Inostroza-Nieves, Alicia Rivera, Jose R. Romero
Summary: A study found that Major Histocompatibility Complex (MHC) molecules play a role in Sickle Cell Disease (SCD) pathophysiology. Endothelial cells express MHC molecules after exposure to cytokines. SCD is characterized by vascular endothelial cell activation, oxidative stress, sickle cell adhesion, and excess levels of endothelin-1 (ET-1). The study suggests that ET-1 is a novel regulator of MHC class II molecules and ET-1 receptor blockade may be a promising therapeutic approach for regulating immune and vascular responses in SCD.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Biotechnology & Applied Microbiology
Angela Chiew Wen Ch'ng, Paula Lam, Mohammed Alassiri, Theam Soon Lim
Summary: The immune system relies on B- and T-lymphocytes, antibodies, and T-cell receptors to protect the body from invading threats. Antibodies have a more direct role in target recognition compared to T-cell receptors. Despite challenges in displaying TCR on phage surfaces, recombinant versions and modifications have been introduced to facilitate TCR development in phage display.
BIOTECHNOLOGY ADVANCES
(2022)
Article
Immunology
Brendan W. MacNabb, Sravya Tumuluru, Xiufen Chen, James Godfrey, Darshan N. Kasal, Jovian Yu, Marlieke L. M. Jongsma, Robbert M. Spaapen, Douglas E. Kline, Justin Kline
Summary: This study demonstrates the importance of MHC-I cross-dressing in regulating anti-tumor immunity. In addition to quantitatively enhancing tumor antigen presentation, it also enables dendritic cells to more accurately mirror the cancer cell peptidome.
Article
Biology
Qingxiu Hu, Xiaoqi Huang, Yabin Jin, Rui Zhang, Aimin Zhao, Yiping Wang, Chenyun Zhou, Weixin Liu, Xunwei Liu, Chunhua Li, Guangyi Fan, Min Zhuo, Xiaoning Wang, Fei Ling, Wei Luo
Summary: This study provides the first physical mapping of MHC and KIR gene regions in Vietnamese cynomolgus macaques. It identifies four functional Mafa-B loci and high-frequency alleles. These findings contribute to the precise selection of animals with specific genetic markers for future medical research.
Article
Ecology
Marie L. Nydam, Alan R. Lemmon, Emily M. Lemmon, Kevin Ziegler, C. Sarah Cohen, Lilian A. Palomino-Alvarez, Carmela Gissi
Summary: This study explores the evolution of allorecognition types in the colonial ascidians called botryllids and reveals hidden diversity within this group through the reconstruction of a phylogenomic tree. The results suggest that certain types of allorecognition reactions could be ancestral to certain groups of botryllids, and the existence of previously unknown species is demonstrated.
FRONTIERS IN ECOLOGY AND EVOLUTION
(2023)
Article
Biochemistry & Molecular Biology
Rajitha T. Rajeshwar, Jeremy C. Smith
Summary: The diversity in alpha beta T-cell receptor (TCR) sequences and structures makes it challenging to analyze the specificity and sensitivity determining T-cell immunogenicity. By analyzing the structures of TCRs bound to human class I nonamer peptide-MHC complexes, it is found that residues at peptide positions 4-8 are particularly important for TCR binding. This analysis provides insights for the structural modeling of TCR:pMHC complexes and has implications for the design of peptide-based vaccines and T-cell-based immunotherapies.
PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS
(2022)
Review
Genetics & Heredity
Martin Plasil, Jan Futas, April Jelinek, Pamela A. Burger, Petr Horin
Summary: This review provides a summary of the current knowledge on the major histocompatibility complex (MHC) in the family Felidae. Despite the potential for studying the biological functions of MHC genes in disease mechanisms and adaptation, our understanding of the MHC in the Felidae is fragmentary and based mainly on studies of the domestic cat and selected big cats. The structure and conservation of the MHC region in felids show similarities to those of other mammals, but there are some differences in gene contents. Further research is needed to explore the functional significance of felid MHC genes, particularly in relation to disease and conservation.
FRONTIERS IN GENETICS
(2022)
Article
Pharmacology & Pharmacy
Natsumi Mizuno, Yoshiki Yanagawa
Summary: In this study, it was found that tofacitinib enhanced IFN-gamma-induced MHC II expression in macrophages by transcriptional regulation through induction of CIITA, while decreasing the expression of CD86.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2022)
Review
Immunology
Heather F. Jones, Zaki Molvi, Martin G. Klatt, Tao Dao, David A. Scheinberg
Summary: This review summarizes the development of TCR-based therapeutic strategies in the past three decades, highlighting exciting opportunities for further utilizing TCR recognition for therapeutic benefit, but emphasizing the balance between efficacy and potency versus specificity and potential toxicity of these new therapeutic modalities.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Genetics & Heredity
Dong Chen, Yanjuan Li
Summary: The major histocompatibility complex (MHC) is a crucial locus on vertebrate DNA encoding cell surface proteins that play a key role in the adaptive immune system. An effective predictor called PredMHC was developed to identify MHC from protein sequences using a combination of features and classifiers. Experimental results demonstrated the accuracy and effectiveness of PredMHC in predicting MHC.
FRONTIERS IN GENETICS
(2022)
Article
Biology
Prithvi R. Pandey, Bartosz Rozycki, Reinhard Lipowsky, Thomas R. Weikl
Summary: In this study, extensive atomistic molecular dynamics simulations were used to investigate the structural and orientational variability of the membrane-embedded T cell receptor (TCR) - CD3 complex based on the recent cryo-EM structure. It was found that the TCR extracellular (EC) domain exhibits a high degree of variability in orientation, which is coupled to domain rotation and characteristic changes throughout the TCR - CD3 complex. The simulations provided insights into the conformational changes of the complex in response to tilt-inducing forces on antigen-bound TCRs.
Article
Biochemistry & Molecular Biology
Yuying Sun, Fang Yuan, Ling Wang, Dongfa Dai, Zhijian Zhang, Fei Liang, Nan Liu, Juan Long, Xiao Zhao, Yongzhi Xi
Summary: This study generated fine-scale maps of MHC recombination and de novo mutations in Han Chinese families, revealing recombination hotspots and Han-specific breakpoints. The MHC de novo mutation rate was found to be higher than the genome-wide de novo mutation rate, and the polymorphisms generated by mutation and recombination were located within and outside linkage disequilibrium regions of the MHC, respectively. The evolution of the MHC locus was mainly controlled by positive selection.
JOURNAL OF GENETICS AND GENOMICS
(2022)
Article
Oncology
Naman Sharma, Patrick M. Reagan, Jane L. Liesveld
Summary: CAR-T immunotherapy, a new treatment modality, modifies the patient's T cells to recognize and kill cancer cells. However, it comes with immune side effects such as cytokine release syndrome and prolonged cytopenia. This review summarizes clinical trials, mechanisms, and interventions on prolonged cytopenia post CAR-T infusion.
Article
Immunology
Valentina Ceglia, Erin J. Kelley, Annalee S. Boyle, Sandra Zurawski, Heather L. Mead, Caroline E. Harms, Jean-Philippe Blanck, Anne-Laure Flamar, Jung Hwa Kirschman, Paul Ogongo, Joel D. Ernst, Yves Levy, Gerard Zurawski, John A. Altin
Summary: This study demonstrates a method that combines antigen-driven expansion, deep TCR sequencing, and a novel analysis framework to confidently identify homologous 'Clusters of Expanded TCRs (CETs)' without cell isolation and assign them to specific antigens. It shows that clonotypes within each CET respond to the same epitope, and that protein antigens can stimulate multiple CETs reactive to constituent peptides. The method may be used to monitor T cell responses to vaccination and immunotherapy with high fidelity.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Genetics & Heredity
Erick Velastegui, Edwin Vera, Wim Vanden Berghe, Mindy S. Munoz, Andrea Orellana-Manzano
Summary: HLA-C, located within the major histocompatibility complex, has become a prominent target in biomedical research due to its involvement in various diseases. The interaction between HLA-C and KIR is crucial for immune responses, particularly in viral infections. This review provides an overview of the structure, origin, function, and pathological implications of HLA-C, highlighting its genetic variations and susceptibility to epigenetic modifications.
FRONTIERS IN GENETICS
(2023)
Article
Immunology
Shivam K. Purohit, Carolyn Samer, Hamish E. G. McWilliam, Renee Traves, Megan Steain, Brian P. McSharry, Paul R. Kinchington, David C. Tscharke, Jose A. Villadangos, Jamie Rossjohn, Allison Abendroth, Barry Slobedman
Summary: This study demonstrates that varicella zoster virus suppresses the expression of antigen presentation molecule MR1, highlighting the intricate temporal relationship between infection and ligand availability. The study also suggests that VZV likely encodes multiple viral genes targeting MR1.
JOURNAL OF INFECTIOUS DISEASES
(2023)
Article
Multidisciplinary Sciences
Marcin Wegrecki, Tonatiuh A. Ocampo, Sachith D. Gunasinghe, Anouk von Borstel, Shin Yi Tin, Josephine F. Reijneveld, Thinh-Phat Cao, Benjamin S. Gully, Jerome Le Nours, D. Branch Moody, Ildiko Van Rhijn, Jamie Rossjohn
Summary: In this study, the authors reveal a novel geometrically alternate sideways mode of recognition of the antigen-presenting molecule CD1a by a gamma delta T cell receptor. The gamma delta TCR binds CD1a in a lipid-independent manner and induces clustering of TCRs and T cell signaling.
NATURE COMMUNICATIONS
(2022)
Article
Cell Biology
Hui Jing Lim, Jacinta M. Wubben, Cristian Pinero Garcia, Sebastian Cruz-Gomez, Jieru Deng, Jeffrey Y. W. Mak, Abderrahman Hachani, Regan J. Anderson, Gavin F. Painter, Jesse Goyette, Shanika L. Amarasinghe, Matthew E. Ritchie, Antoine Roquilly, David P. Fairlie, Katharina Gaus, Jamie Rossjohn, Jose A. Villadangos, Hamish E. G. McWilliam
Summary: MR1 is a conserved microbial immune-detection system in mammals that presents antigens to specific lymphocytes, contributing to host defense and tissue repair. This study reveals that human MR1 interacts with the endocytic adaptor protein 2 (AP2) complex to regulate its internalization from the cell surface, thus controlling antigen presentation and microbial metabolic detection.
JOURNAL OF CELL BIOLOGY
(2022)
Article
Immunology
Michael N. T. Souter, Wael Awad, Shihan Li, Troi J. Pediongco, Bronwyn S. Meehan, Lucy J. Meehan, Zehua Tian, Zhe Zhao, Huimeng Wang, Adam Nelson, Jerome Le Nours, Yogesh Khandokar, T. Praveena, Jacinta Wubben, Jie Lin, Lucy C. Sullivan, George O. Lovrecz, Jeffrey Y. W. Mak, Ligong Liu, Lyudmila Kostenko, Katherine Kedzierska, Alexandra J. Corbett, David P. Fairlie, Andrew G. Brooks, Nicholas A. Gherardin, Adam P. Uldrich, Zhenjun Chen, Jamie Rossjohn, Dale I. Godfrey, James McCluskey, Daniel G. Pellicci, Sidonia B. G. Eckle
Summary: Souter et al. demonstrate that the CD8-MR1 interaction enhances antigen recognition and functional responses of MAIT cells, and is critical for the recognition of folate-derived antigens by other MR1-reactive T cells.
JOURNAL OF EXPERIMENTAL MEDICINE
(2022)
Article
Cell Biology
Anouk von Borstel, Thi H. O. Nguyen, Louise C. Rowntree, Thomas M. Ashhurst, Lilith F. Allen, Lauren J. Howson, Natasha E. Holmes, Olivia C. Smibert, Jason A. Trubiano, Claire L. Gordon, Allen C. Cheng, Stephen J. Kent, Jamie Rossjohn, Katherine Kedzierska, Martin S. Davey
Summary: SARS-CoV-2 infection can cause severe COVID-19 in some individuals. The immune system, particularly effector gamma delta T cells, plays a role in the defense against SARS-CoV-2. Our study shows an association between effector populations of gamma delta T cells and acute COVID-19 in unvaccinated individuals.
IMMUNOLOGY AND CELL BIOLOGY
(2023)
Article
Immunology
Gwennaelle C. Monnot, Marcin Wegrecki, Tan-Yun Cheng, Yi-Ling Chen, Brigitte N. Sallee, Reka Chakravarthy, Ioanna Maria Karantza, Shin Yi Tin, Alexandra E. Khaleel, Isha Monga, Laura N. Uwakwe, Alice Tillman, Bin Cheng, Soundos Youssef, Soo Weei Ng, Adam Shahine, Javier A. Garcia-Vilas, Anne-Catrin Uhlemann, Lindsey A. Bordone, Arnold Han, Christine H. Rohde, Graham Ogg, D. Branch Moody, Jamie Rossjohn, Annemieke de Jong
Summary: CD1a presents a range of self-lipid antigens found within the skin. The study identifies CD1a-dependent T cell responses to bacterial membrane phospholipids and suggests a link between PG-based lipid-activated T cells and atopic dermatitis pathogenesis. The expansion of CD4(+) CD1a-(lysyl)PG tetramer(+) T cells in patients with atopic dermatitis supports the involvement of bacteria-associated lipids in the development of this condition.
Article
Cell Biology
Timothy Patton, Zhe Zhao, Xin Yi Lim, Eleanor Eddy, Huimeng Wang, Adam G. Nelson, Bronte Ennis, Sidonia B. G. Eckle, Michael N. T. Souter, Troi J. Pediongco, Hui-Fern Koay, Jian-Guo Zhang, Tirta M. Djajawi, Cynthia Louis, Najoua Lalaoui, Nicolas Jacquelot, Andrew M. Lew, Daniel G. Pellicci, James McCluskey, Yifan Zhan, Zhenjun Chen, Kate E. Lawlor, Alexandra J. Corbett
Summary: Cell death mechanisms in T lymphocytes vary depending on their developmental stage, cell subset, and activation status. However, the cell death control mechanisms of mucosal-associated invariant T (MAIT) cells, a specialized T cell population, are not well understood. In this study, it was found that MAIT cells express high levels of key necroptotic machinery, RIPK3 and MLKL proteins. Surprisingly, the loss of RIPK3, but not MLKL or caspase-8, specifically increased the abundance of MAIT cells in various organs, indicating a cell-intrinsic regulation of MAIT cell accumulation by RIPK3 signaling.
CELL DEATH & DISEASE
(2023)
Article
Immunology
Caroline L. Ashley, Brian P. McSharry, Hamish E. G. McWilliam, Richard J. Stanton, Ceri A. Fielding, Rommel A. Mathias, David P. Fairlie, James McCluskey, Jose A. Villadangos, Jamie Rossjohn, Allison Abendroth, Barry Slobedman
Summary: This study reveals that human cytomegalovirus (HCMV) inhibits the MR1 pathway and disrupts the MR1:MAIT cell axis through the viral protein gpUS9. The interaction between this virus and MAIT cells in the context of viral infection is not well characterized.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Allergy
Nicole A. A. Mifsud, Patricia T. T. Illing, Rebecca Ho, Johanna E. E. Tuomisto, Heidi Fettke, Kerry A. A. Mullan, James McCluskey, Jamie Rossjohn, Julian Vivian, Rangsima Reantragoon, Anthony W. W. Purcell
Summary: Allopurinol is a drug used in the treatment of gout but can cause severe and life-threatening hypersensitivity reactions. People carrying the HLA-B*58:01 allotype are at higher risk. The drug metabolite oxypurinol is responsible for T cell-mediated immunopathology, and the TCR repertoire usage of reactive T cells in ALP-induced hypersensitivity reactions has been limitedly studied. This research shows that oxypurinol drives CD8(+) T cell responses and that drug-exposed memory T cells exhibit a proinflammatory immunophenotype. The study also supports the concept of pharmacological interaction with immune receptors and highlights oligoclonal and private clonotypic profiles of OXP-induced TCRs.
Review
Immunology
Wael Awad, Lisa Ciacchi, James McCluskey, David P. Fairlie, Jamie Rossjohn
Summary: Metabolite-based T-cell immunity plays a crucial role in antimicrobial immunity, autoimmunity, and cancer. This review summarizes the impact of metabolite recognition and modulation on mucosal-associated invariant T cells (MAIT), providing a framework for understanding the molecular correlates of MAIT T cell receptor (TCR)-MR1 recognition.
CURRENT OPINION IN IMMUNOLOGY
(2023)
Article
Immunology
Adam G. Nelson, Huimeng Wang, Phoebe M. Dewar, Eleanor M. Eddy, Songyi Li, Xin Yi Lim, Timothy Patton, Yuchen Zhou, Troi J. Pediongco, Lucy J. Meehan, Bronwyn S. Meehan, Jeffrey Y. W. Mak, David P. Fairlie, Andrew W. Stent, Lars Kjer-Nielsen, James Mccluskey, Sidonia B. G. Eckle, Alexandra J. Corbett, Michael N. T. Souter, Zhenjun Chen
Summary: This study outlines three methods to increase the abundance of mucosal-associated invariant T (MAIT) cells in C57BL/6 mice. The administration of synthetic 5-amino-6-D-ribitylaminouracil (5-A-RU) in combination with inflammatory stimuli has been shown to significantly increase the frequency and absolute numbers of MAIT cells in mice. These increased MAIT cells are functional and can provide protection against lethal infections.
FRONTIERS IN IMMUNOLOGY
(2023)
Meeting Abstract
Immunology
A. Braun, J. Mobbs, S. Anand, J. Tuomisto, S. Z. Chung, E. Hughes, J. Rossjohn, J. P. Vivian, C. Manthey, A. Fourie, M. McKinnon, A. W. Purcell
EUROPEAN JOURNAL OF IMMUNOLOGY
(2022)
Meeting Abstract
Immunology
Wuji Zhang, Lukasz Kedzierski, Brendon Y. Chua, Adam K. Wheatley, Louise Rowntree, Lilith Allen, Jan Petersen, Priyanka Chaurasia, Robert Mettelman, Adrian Miller, Paul G. Thomas, Jamie Rossjohn, Kanta Subbarao, Stephen J. Kent, Jane Nelson, Jane Davies, Thi H. O. Nguyen, Katherine Kedzierska
JOURNAL OF IMMUNOLOGY
(2022)
Article
Immunology
Marcela de Lima Moreira, Luana Oliveira Borges-Fernandes, Marcelo Antonio Pascoal-Xavier, Agata Lopes Ribeiro, Victoria Hellena Silva Pereira, Troi Pediongco, Marcio Sobreira da Silva Araujo, Andrea Teixeira-Carvalho, Andrea Lucchesi de Carvalho, Maria Vitoria Assumpcao Mourao, Flavia Alves Campos, Marineide Borges, Mariangela Carneiro, Zhenjun Chen, Eleanor Saunders, Malcolm McConville, Moriya Tsuji, James McCluskey, Olindo Assis Martins-Filho, Sidonia Barbara Guiomar Eckle, Jordana Grazziela Alves Coelho-dos-Reis, Vanessa Peruhype-Magalhaes
Summary: This study reveals the role of MAIT cells in protecting against visceral leishmaniasis, expanding our understanding of MAIT-cell immunity beyond bacterial and viral infections. The findings highlight the potential of MAIT-cell-based therapeutics and vaccines for the treatment and prevention of parasitic infections.
FRONTIERS IN IMMUNOLOGY
(2022)