Article
Biochemistry & Molecular Biology
James M. Heather, Matthew J. Spindler, Marta Herrero Alonso, Yifang Ivana Shui, David G. Millar, David S. Johnson, Mark Cobbold, Aaron N. Hata
Summary: The study and manipulation of T cell receptors (TCRs) are crucial in immunology research. Stitchr is a software tool that can generate complete TCR coding sequences based on minimal V/J/CDR3 information, increasing the speed and reproducibility of TCR research.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Si-Yi Chen, Tao Yue, Qian Lei, An-Yuan Guo
Summary: TCRdb is a comprehensive human TCR sequences database, containing over 277 million highly reliable TCR sequences from over 8265 TCR-Seq samples, with unique features including a powerful search function and interactive data visualization charts for comparing TCR repertoire in different samples. It will serve as a valuable resource for the research and application community of T cell immunology.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Gastroenterology & Hepatology
Jazib Uddin, Sunil Tomar, Ankit Sharma, Lisa Waggoner, Varsha Ganesan, Sahiti Marella, Yanfen Yang, Taeko Noah, Simone Vanoni, Andrew Patterson, Chang Zeng, Paul S. Foster, Rodney Newberry, Shrinivas Bishu, John Y. Kao, Michael J. Rosen, Lee Denson, Philip D. King, Kasper Hoebe, Senad Divanovic, Ariel Munitz, Simon P. Hogan
Summary: The inhibitory receptor PIR-B plays a role in regulating CD4(+) IL17a(+) T-cell pathogenic memory responses, modulating chronic intestinal inflammatory responses and the development of colitis. The downstream axis involving PIR-B, Src-homology region 2 domain-containing phosphatase-1/2, and mammalian target of rapamycin complex 1 signaling is important for CD4(+) IL17a(+) cell survival. Furthermore, transcriptional signatures associated with Th17 cells and tissue resident memory networks were enriched in PIR-B+ murine CD4(+) T cells and human CD4(+) T cells expressing LILRB3, demonstrating the potential significance of PIR-B and its human homologue in inflammatory diseases.
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
(2021)
Article
Oncology
Yi-Lin Chen, Chung-Liang Ho, Chen-Yan Hung, Wan-Li Chen, Chen Chang, Yi-Hsin Hou, Jian-Rong Chen, Pin-Jun Chen, Nan-Haw Chow, Wenya Huang, Ya-Ting Hsu, Tsai-Yun Chen, Tsunglin Liu
Summary: This study analyzed TCR beta sequences in Taiwanese TCL patients and found differences in sensitivity compared to European TCL patients using the BIOMED-2 test. Genetic variations in the BIOMED-2 primer sites were not the reason for this difference. The study suggests that non-recombined TCR beta sequences may be a new target for enhancing TCL diagnosis, and the proposed digital PCR assay showed positive results in TCL patients.
FRONTIERS IN ONCOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Franziska Blaeschke, Yan Yi Chen, Ryan Apathy, Bence Daniel, Andy Y. Chen, Peixin Amy Chen, Katalin Sandor, Wenxi Zhang, Zhongmei Li, Cody T. Mowery, Tori N. Yamamoto, William A. Nyberg, Angela To, Ruby Yu, Raymund Bueno, Min Cheol Kim, Ralf Schmidt, Daniel B. Goodman, Tobias Feuchtinger, Justin Eyquem, Chun Jimmie, Julia Carnevale, Ansuman T. Satpathy, Eric Shifrut, Theodore L. Roth, Alexander Marson
Summary: Chronic stimulation can lead to T cell dysfunction, limiting the effectiveness of cellular immunotherapies. Improved methods are needed to compare synthetic knockin sequences and reprogram cell functions. Modular pooled knockin screening was developed, allowing the construction of DNA libraries that identified a transcription factor TFAP4, which enhanced the fitness and anti-cancer function of CAR-T cells. The modularity of the platform facilitated the discovery of complex gene constructs to program cellular functions.
Article
Biochemical Research Methods
Shiva Dahal-Koirala, Gabriel Balaban, Ralf Stefan Neumann, Lonneke Scheffer, Knut Erik Aslaksen Lundin, Victor Greiff, Ludvig Magne Sollid, Shuo-Wang Qiao, Geir Kjetil Sandve
Summary: The development of a novel computational pipeline called TCRpower allows for quantifying the statistical detection power of TCR sequencing methods, enabling reliable detection of disease-relevant TCRs for diagnostic applications.
BRIEFINGS IN BIOINFORMATICS
(2022)
Review
Immunology
Anna Pasetto, Yong-Chen Lu
Summary: T cells are essential in immune responses and cancer immunotherapy. Single-cell sequencing techniques have enabled scientists to study T cells at a deeper level, including T-cell receptor and transcriptome analysis. These techniques also aid in the identification of T-cell neoantigens, advancing T-cell mediated cancer therapy.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Hematology
Paolo Strati, Sairah Ahmed, Fateeha Furqan, Luis E. Fayad, Hun J. Lee, Swaminathan P. Iyer, Ranjit Nair, Loretta J. Nastoupil, Simrit Parmar, Maria A. Rodriguez, Felipe Samaniego, Raphael E. Steiner, Michael Wang, Chelsea C. Pinnix, Sandra B. Horowitz, Lei Feng, Ryan Sun, Catherine M. Claussen, Misha C. Hawkins, Nicole A. Johnson, Prachee Singh, Haleigh Mistry, Swapna Johncy, Sherry Adkins, Partow Kebriaei, Elizabeth J. Shpall, Michael R. Green, Christopher R. Flowers, Jason Westin, Sattva S. Neelapu
Summary: For patients with relapsed or refractory large B-cell lymphoma undergoing CAR T-cell therapy, the use of corticosteroids for toxicity management may impact clinical outcomes. Higher cumulative dose, prolonged duration, and early initiation of corticosteroids were associated with shorter progression-free and overall survival.
Article
Immunology
Josephine R. Giles, Sasikanth Manne, Elizabeth Freilich, Derek A. Oldridge, Amy E. Baxter, Sangeeth George, Zeyu Chen, Hua Huang, Lakshmi Chilukuri, Mary Carberry, Lydia Giles, Nan-Ping P. Weng, Regina M. Young, Carl H. June, Lynn M. Schuchter, Ravi K. Amaravadi, Xiaowei Xu, Giorgos C. Karakousis, Tara C. Mitchell, Alexander C. Huang, Junwei Shi, E. John Wherry
Summary: This study generated an epigenetic and transcriptional atlas of T cell differentiation from healthy humans and applied it to explore disease-specific biology. The study identified molecular regulations of gene expression and chromatin accessibility during T cell differentiation and provided insights into disease biology through three research settings. The study also successfully predicted genome-wide cis-regulatory elements and validated the approach for functional annotation of key effector genes, demonstrating the potential of identifying targets for non-coding cellular engineering.
Review
Biochemistry & Molecular Biology
Xinjie Lu
Summary: This review discusses the structural features and functions of TIM-3 and its role in mediating immune responses in different cell types, as well as the rationale for targeting TIM-3 in cancer immunotherapy. TIM-3 has emerged as a potential biomarker in cancer immunotherapy.
CURRENT MEDICINAL CHEMISTRY
(2022)
Article
Multidisciplinary Sciences
Maryam A. Y. Al-Nesf, Houari B. Abdesselem, Ilham Bensmail, Shahd Ibrahim, Walaa A. H. Saeed, Sara S. Mohammed, Almurtada Razok, Hashim Alhussain, Reham M. A. Aly, Muna Al Maslamani, Khalid Ouararhni, Mohamad Y. Khatib, Ali Ait Hssain, Ali S. Omrani, Saad Al-Kaabi, Abdullatif Al Khal, Asmaa A. Al-Thani, Waseem Samsam, Abdulaziz Farooq, Jassim Al-Suwaidi, Mohammed Al-Maadheed, Heba H. Al-Siddiqi, Alexandra E. Butler, Julie Decock, Vidya Mohamed-Ali, Fares Al-Ejeh
Summary: This study utilizes plasma proteomics to identify risk factors and candidate drugs for predicting COVID-19 severity and patient survival. The findings have significant implications for personalized management of SARS-CoV-2 infected patients.
NATURE COMMUNICATIONS
(2022)
Article
Immunology
Zihang Chen, Qiqi Zhu, Xueqin Deng, Wenqing Yao, Wenyan Zhang, Weiping Liu, Yuan Tang, Sha Zhao
Summary: CD8-predominant AITL is a distinct immune pattern of AITL characterized by anti-tumor immunity impairment and an immunosuppressive microenvironment. CD8-predominant AITL shows significant differences compared to common AITL in terms of clinical and pathological features, TIL subsets, immunoglobulin heavy chain (IGH) repertoires, and gene expression profiles. These characteristics may explain its severe clinical manifestations and poor prognosis.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Multidisciplinary Sciences
Samyuktha Ramesh, Soohyung Park, Wonpil Im, Melissa J. Call, Matthew E. Call
Summary: The B cell receptor (BCR) and T cell receptor (TCR) share a common core transmembrane (TM) structure, which is vital for optimal receptor assembly and stability in the cell membrane.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Review
Immunology
Joerg Christoph Prinz
Summary: HLA-associated autoimmune diseases are likely caused by T-cell-mediated autoimmune responses against self-peptides presented by HLA molecules. Limited knowledge of autoantigens hinders the understanding of autoimmune pathogenesis due to antigen processing complexity and T-cell receptor polyspecificity. In HLA-class I-associated diseases, autoimmune responses target cells expressing parental proteins, while in HLA-class II-associated diseases, immunogenic peptides can originate from both extracellular and cellular self-proteins.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Fisheries
Weijie Chen, Jing Hu, Jianchang Huang, Qin Liu, Qiyao Wang, Yuanxing Zhang, Dahai Yang
Summary: In this study, the genomic organization of T-cell receptors (TCR) and immunoglobulin heavy chains (IgHs) in turbot were investigated and annotated for the first time using Isoform-sequencing. Single-cell RNA sequencing confirmed the high expression of these genes in T and B cell clusters and identified differential gene expression profiles and potential functions of IgM+IgD+ B cells and IgT+ B cells.
FISH & SHELLFISH IMMUNOLOGY
(2023)
Review
Immunology
James E. Crowe
Summary: Antibodies have been widely used for preventing and treating viral infections since the nineteenth century, and the development of potent human monoclonal antibodies has paved the way for unprecedented activities. Modifications that extend antibody half-life and the clinical development of broad and potent antibodies have the potential to make antibodies the principal tool in managing future viral epidemics. Furthermore, these antibodies are crucial for research and developing effective vaccines.
ANNUAL REVIEW OF IMMUNOLOGY
(2022)
Editorial Material
Microbiology
James E. Crowe, Robert H. Carnahan
Summary: The paper provides a comprehensive investigation into the molecular and functional basis of 17D vaccine responses, as well as the differences in antibody neutralization between the 17D and related African lineage strains and contemporary Central/South American strains.
CELL HOST & MICROBE
(2022)
Article
Multidisciplinary Sciences
Liya Hu, Wilhelm Salmen, Rong Chen, Yi Zhou, Frederick Neill, James E. Crowe, Robert L. Atmar, Mary K. Estes, B. V. Venkataram Prasad
Summary: This study reveals the structure and features of human norovirus GII.4 virus-like particles using X-ray crystallography and cryo-EM. It uncovers the adaptability and stability of the capsid protein VP1, as well as its potential antigen presentation mechanism, providing valuable insights for vaccine development.
NATURE COMMUNICATIONS
(2022)
Article
Cell Biology
Jennifer M. Pfaff-Kilgore, Edgar Davidson, Kathryn Kadash-Edmondson, Mayda Hernandez, Erin Rosenberg, Ross Chambers, Matteo Castelli, Nicola Clementi, Nicasio Mancini, Justin R. Bailey, James E. Crowe, Mansun Law, Benjamin J. Doranz
Summary: The E1 and E2 envelope proteins of hepatitis C virus (HCV) form a surprisingly fragile complex where even a single alanine mutation at 92% of positions disrupts its function. The identified amino-acid-level targets are highly conserved and functionally critical, providing potential opportunities for improved therapies and vaccines against hepatitis C.
Article
Microbiology
Clara T. Schoeder, Pavlo Gilchuk, Amandeep K. Sangha, Kaitlyn V. Ledwitch, Delphine C. Malherbe, Xuan Zhang, Elad Binshtein, Lauren E. Williamson, Cristina E. Martina, Jinhui Dong, Erica Armstrong, Rachel Sutton, Rachel Nargi, Jessica Rodriguez, Natalia Kuzmina, Brooke Fiala, Neil P. King, Alexander Bukreyev, James E. Crowe, Jens Meiler
Summary: This study presents the design and functional validation of an epitope-focused immunogen based on the HR2-MPER epitope of the ebolavirus. The results demonstrate the capabilities and challenges of computational epitope-focused vaccine design, and provide insights for the rational design of immunogens against ebolavirus.
Article
Multidisciplinary Sciences
Sandhya Bangaru, Aleksandar Antanasijevic, Nurgun Kose, Leigh M. Sewall, Abigail M. Jackson, Naveenchandra Suryadevara, Xiaoyan Zhan, Jonathan L. Torres, Jeffrey Copps, Alba Torrents de la Pena, James E. Crowe, Andrew B. Ward
Summary: This study investigated the antibody specificity against seasonal coronaviruses and SARS-CoV-2 in serum samples. The results showed that preexisting immunity contained antibodies specific to seasonal coronaviruses, while convalescent serum exhibited reactivity to all coronaviruses. Epitope mapping revealed differential targeting of epitopes by preexisting antibodies and convalescent serum antibodies.
Article
Multidisciplinary Sciences
Nina G. Bozhanova, Andrew Flyak, Benjamin P. Brown, Stormy E. Ruiz, Jordan Salas, Semi Rho, Robin G. Bombardi, Luke Myers, Cinque Soto, Justin R. Bailey, James E. Crowe, Pamela J. Bjorkman, Jens Meiler
Summary: Despite the success of antiviral treatment for HCV, the development of an HCV vaccine is still necessary to prevent reinfection, drug-resistant strains, and provide protection for individuals without access to antiviral therapy. This study identifies new antibodies with a specific structural motif that could inform future vaccine design.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Lauren E. Williamson, Abhishek Bandyopadhyay, Kevin Bailey, Devika Sirohi, Thomas Klose, Justin G. Julander, Richard J. Kuhn, James E. Crowe
Summary: This report presents cryo-electron microscopy reconstructions of three neutralizing human monoclonal antibodies against Eastern equine encephalitis virus (EEEV), and analyzes the factors contributing to the differences in their neutralization potencies. Structural and biophysical insights are provided, which can inform the design of candidate vaccines and therapeutic antibodies for all icosahedral viruses.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Cell Biology
Saravanan Raju, Lucas J. Adams, James T. Earnest, Kelly Warfield, Lo Vang, James E. Crowe Jr, Daved H. Fremont, Michael S. Diamond
Summary: By analyzing samples from a phase 2 clinical trial, researchers found that the PXVX0317 vaccine induced high levels of neutralizing antibodies and circulating antigen-specific B cells against chikungunya virus. Monoclonal antibodies generated from peripheral blood B cells of vaccinated individuals demonstrated potent neutralization of CHIKV and related arthritogenic alphaviruses. These findings highlight the inhibitory breadth and activity of the B cell response induced by the PXVX0317 vaccine against CHIKV and potentially other related alphaviruses.
SCIENCE TRANSLATIONAL MEDICINE
(2023)
Article
Microbiology
Robert Stass, Taylor B. Engdahl, Nathaniel S. Chapman, Rachael M. Wolters, Laura S. Handal, Summer M. Diaz, James E. Crowe, Thomas A. Bowden
Summary: This study identifies a highly neutralizing human monoclonal antibody, SNV-42, that interferes with receptor recognition and fusion during hantavirus host-cell entry. Structural analysis reveals the mechanism by which SNV-42 binds to the Gn-Gc heterodimer lattice and inhibits viral infection, providing a blueprint for understanding the human neutralizing antibody response to hantavirus infection.
NATURE MICROBIOLOGY
(2023)
Article
Multidisciplinary Sciences
Cynthia M. McMillen, Nathaniel S. Chapman, Ryan M. Hoehl, Lauren B. Skvarca, Madeline M. Schwarz, Laura S. Handal, James E. Crowe Jr, Amy L. Hartman
Summary: The authors demonstrate in rodent models that a neutralizing monoclonal antibody can prevent vertical transmission of RVFV both before and after infection. RVFV is an emerging mosquito-transmitted virus that circulates in livestock and humans in Africa and the Middle East. The antibody reduces viral replication and provides protection against RVFV infection and vertical transmission in both dams and offspring.
NATURE COMMUNICATIONS
(2023)
Article
Medicine, Research & Experimental
Nicole Frumento, Alexis Figueroa, Tingchang Wang, Muhammad N. Zahid, Shuyi Wang, Guido Massaccesi, Georgia Stavrakis, James E. Crowe, Andrew Flyak, Hongkai Ji, Stuart C. Ray, George M. Shaw, Andrea L. Cox, Justin R. Bailey
Summary: This study investigated the development of broadly neutralizing antibodies (bNAbs) in HCV-infected individuals, including those with persistent infection or spontaneous clearance of multiple reinfections. The findings showed that the breadth and potency of the antibody response increased with exposure to genetically distinct infections and longer duration of viremia. Importantly, repeated exposure to antigenically related, antibody-sensitive envelope proteins was associated with potent bNAb induction. These results suggest that a prime-boost vaccine strategy with genetically distinct, antibody-sensitive viruses could be a promising approach to inducing potent bNAbs in humans.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
Article
Medicine, Research & Experimental
Ronald R. Cobb, Joseph Nkolola, Pavlo Gilchuk, Abishek Chandrashekar, Jingyou Yu, Robert House, Christopher G. Earnhart, Nicole M. Dorsey, Svetlana A. Hopkins, Doris M. Snow, Rita E. Chen, Laura A. VanBlargan, Manuel Hechenblaickner, Brian Hoppe, Laura Collins, Milan T. Tomic, Genevieve H. Nonet, Kyal Hackett, James C. Slaughter, Mark G. Lewis, Hanne Andersen, Anthony Cook, Michael S. Diamond, Robert H. Carnahan, Dan H. Barouch, James E. Crowe
Summary: This study demonstrates that neutralizing antibodies with extended half-life and lacking Fc-mediated effector functions are highly effective for pre-exposure prophylaxis of SARS-CoV-2 infection in NHPs, supporting the clinical development of ADM03820 for COVID-19 prevention.
Article
Medicine, Research & Experimental
Naveenchandra Suryadevara, Andrea R. Shiakolas, Laura A. VanBlargan, Elad Binshtein, Rita E. Chen, James Brett Case, Kevin J. Kramer, Erica C. Armstrong, Luke Myers, Andrew Trivette, Christopher Gainza, Rachel S. Nargi, Christopher N. Selverian, Edgar Davidson, Benjamin J. Doranz, Summer M. Diaz, Laura S. Handal, Robert H. Carnahan, Michael S. Diamond, Ivelin S. Georgiev, James E. Crowe
Summary: This study identifies a rare human antibody, COV23434, that disrupts the integrity of the SARS-CoV-2 S protein and possesses a distinct class of functional activity. The findings suggest that the trimer interface region of the S protein may be a vulnerable site for the virus.
JOURNAL OF CLINICAL INVESTIGATION
(2022)