Article
Immunology
Yuri Poluektov, Marybeth George, Pirouz Daftarian, Marc C. Delcommenne
Summary: The study focuses on evaluating the binding affinities of SARS-CoV-2 peptides to different MHC alleles using the QuickSwitchTM platform, identifying multiple MHC binders with high promiscuity. These results provide important data for further research on the SARS-CoV-2 virus and its antigenic epitopes.
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
Medicine, Research & Experimental
Claire Lhuillier, Nils-Petter Rudqvist, Takahiro Yamazaki, Tuo Zhang, Maud Charpentier, Lorenzo Galluzzi, Noah Dephoure, Cristina C. Clement, Laura Santambrogio, Xi Kathy Zhou, Silvia C. Formenti, Sandra Demaria
Summary: Radiotherapy upregulates the expression of genes containing immunogenic mutations, enhancing the therapeutic efficacy of neoantigen vaccination by promoting the killing of tumor cells through CD8 and CD4 T cells. CD4 T cells produce Th1 cytokines to promote epitope spread, while utilizing radiation to enhance the ability of MHC molecules and death receptors on tumor cells.
JOURNAL OF CLINICAL INVESTIGATION
(2021)
Review
Immunology
Brendan K. Reed, John W. Kappler
Summary: The search for T cell antigens driving T1D has been ongoing for over three decades. Recent research has revealed that many important MHCII-presented epitopes are actually fusions of peptide fragments from different proteins, attributed to a process called reverse proteolysis.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Amanda M. Honan, Emily N. Vazquez, Zhibin Chen
Summary: The study revealed that CD8(+) T cells can convert to CD4(+) T cells in mice, resulting in a unique population of MHC-I-restricted CD4(+) T cells. This conversion process is influenced by MHC-II expression in lymph node stromal cells and involves a specific transcriptional switch. In vitro expansion of CI-T-reg cells using LNSCs showed potential for therapeutic applications in suppressing inflammatory tissue damage.
JOURNAL OF IMMUNOLOGY
(2021)
Article
Immunology
Brendan Reed, Frances Crawford, Ryan C. Hill, Niyun Jin, Janice White, S. Harsha Krovi, Philippa Marrack, Kirk Hansen, John W. Kappler
Summary: The identification of peptide epitopes presented by MHCII molecules that drive CD4 T cell autoimmunity, particularly in type 1 diabetes, has been a challenge. Recent insights suggest that important epitopes are actually chimeric epitopes pieced together from different peptide fragments, rather than directly processed from a protein source. This fusion process, known as transpeptidation, may occur during the catabolic turnover of pancreatic proteins, shedding light on how self-tolerance can be broken peripherally in autoimmune diseases like T1D.
JOURNAL OF EXPERIMENTAL MEDICINE
(2021)
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
Leila Fonderflick, Timothee Baudu, Olivier Adotevi, Michael Guittaut, Pascale Adami, Regis Delage-Mourroux
Summary: Vaccine therapy is a promising method of research to promote T cell immune response and to develop novel antitumor immunotherapy protocols. Increasing evidence shows that autophagy plays a role in antigen processing and presentation to T cells.
Article
Biotechnology & Applied Microbiology
Kenji Sugata, Yukiko Matsunaga, Yuki Yamashita, Munehide Nakatsugawa, Tingxi Guo, Levon Halabelian, Yota Ohashi, Kayoko Saso, Muhammed A. Rahman, Mark Anczurowski, Chung-Hsi Wang, Kenji Murata, Hiroshi Saijo, Yuki Kagoya, Dalam Ly, Brian D. Burt, Marcus O. Butler, Tak W. Mak, Naoto Hirano
Summary: By combining molecular biological and immunological techniques, this study successfully cloned sequences encoding HLA-DP, HLA-DQ, and HLA-DR molecules with enhanced CD4 binding affinity and produced affinity-matured class II dimers that stain antigen-specific T cells better than conventional multimers. These affinity-matured class II dimers will aid in the investigation of human CD4(+) T-cell responses, providing a comprehensive library of dimers for HLA-DP, HLA-DQ, and HLA-DR alleles. The readily detectable CD4(+) T cells with class II MHC dimers are crucial for studying human immune responses.
NATURE BIOTECHNOLOGY
(2021)
Article
Multidisciplinary Sciences
Adham S. Bear, Tatiana Blanchard, Joseph Cesare, Michael J. Ford, Lee P. Richman, Chong Xu, Miren L. Baroja, Sarah McCuaig, Christina Costeas, Khatuna Gabunia, John Scholler, Avery D. Posey, Mark H. O'Hara, Anze Smole, Daniel J. Powell, Benjamin A. Garcia, Robert H. Vonderheide, Gerald P. Linette, Beatriz M. Carreno
Summary: Activating RAS missense mutations are common in human cancers and can be immunologically targeted. By characterizing HLA class I-restricted mKRAS epitopes, the study successfully isolated and transferred mKRAS-specific TCR to CD8(+) T cells, demonstrating cytotoxicity against mKRAS tumor cells from various origins, with lytic activity correlating with peptide-HLA class I complex abundance. Adoptive transfer of mKRAS-TCR engineered CD8(+) T cells led to tumor eradication in a xenograft model, validating mKRAS peptides as epitopes for immune therapies.
NATURE COMMUNICATIONS
(2021)
Article
Immunology
Yue Shen, Jerry M. Parks, Jeremy C. Smith
Summary: This study presents a method for classifying HLA class I molecules using three-dimensional structures, which improves the breadth, accuracy, stability, and flexibility of classification. The findings show that structural similarity is highly correlated with peptide binding specificity. This new classification is useful in peptide-based vaccine development and HLA-disease association studies.
JOURNAL OF IMMUNOLOGY
(2023)
Article
Genetics & Heredity
Chloe H. Lee, Jaesung Huh, Paul R. Buckley, Myeongjun Jang, Mariana Pereira Pinho, Ricardo A. Fernandes, Agne Antanaviciute, Alison Simmons, Hashem Koohy
Summary: The study presents a novel computational workflow, TRAP, for accurately predicting CD8 + T-cell epitopes. It outperformed other algorithms in both cancer and pathogenic settings. Additionally, a new metric called RSAT was developed to estimate the immunogenicity of pathogenic peptides.
Article
Immunology
Julien Racle, Philippe Guillaume, Julien Schmidt, Justine Michaux, Amede Larabi, Kelvin Lau, Marta A. S. Perez, Giancarlo Croce, Raphael Genolet, George Coukos, Vincent Zoete, Florence Pojer, Michal Bassani-Sternberg, Alexandre Harari, David Gfeller
Summary: In this study, a dataset of 627,013 unique MHC-II ligands identified by mass spectrometry was collected and curated, allowing for precise determination of binding motifs for 88 MHC-II alleles across different species. Further analysis revealed a reverse-binding mode in HLA-DP ligands, and a machine-learning framework was developed to accurately predict binding specificities and ligands of any MHC-II allele.
Article
Oncology
Hiroko Nakajima, Jun Nakata, Kanako Imafuku, Hiromu Hayashibara, Kazuki Isokawa, Keiko Udaka, Fumihiro Fujiki, Soyoko Morimoto, Kana Hasegawa, Naoki Hosen, Yoshiko Hashii, Sumiyuki Nishida, Akihiro Tsuboi, Yoshihiro Oka, Yusuke Oji, Shinji Sogo, Haruo Sugiyama
Summary: This study identified three novel mouse Th epitope peptides that strongly induced and maintained WT1-specific CTLs, efficiently rejected WT1-expressing tumor cells, and showed that these CTLs played a central role in tumor rejection. The majority of WT1-specific CTLs induced by the co-immunization with WT1 CTL and the WT1-specific Th peptides were effector memory CD8(+) T cells, demonstrating their essential function in WT1-specific tumor immunity.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2021)
Article
Immunology
Artem Mansurkhodzhaev, Camila R. R. Barbosa, Michele Mishto, Juliane Liepe
Summary: This study investigates the effect of proteasome-generated cis-spliced peptides on the anti-viral response of CD8(+) T cells. Despite their high frequency, the cis-spliced peptides we studied are suggested to only marginally impact the variety of functional CD8(+) cytotoxic T cells involved in the response against viruses.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Cell Biology
Caitlin C. Zebley, Rama S. Akondy, Benjamin A. Youngblood, Haydn T. Kissick
Summary: The pool of memory CD8 T cells consists of highly specialized subpopulations of cells with both shared and distinct functions. Current research on T-cell memory focuses on how these subpopulations arise, how the cells are maintained over the host's lifespan, and how they protect the host against reinfection. However, the use of surface markers to define and study these memory T-cell subsets is proving to be inadequate, and there is a need for an updated definition using the epigenetic state of cells to better characterize the functional capacity of CD8 memory T-cell subsets.
COLD SPRING HARBOR PERSPECTIVES IN BIOLOGY
(2022)
Meeting Abstract
Oncology
Mehmet Asim Bilen, Yuan Liu, Bassel Nazha, Jacqueline T. Brown, Adeboya O. Osunkoya, Sierra Williams, Wilena Session, Lauren Beth Yantorni, Greta Russler, Sarah Caulfield, Shreyas S. Joshi, Vikram M. Narayan, Christopher Paul Filson, Kenneth Ogan, Omer Kucuk, Bradley Curtis Carthon, Haydn Kissick, Viraj A. Master
JOURNAL OF CLINICAL ONCOLOGY
(2022)
Meeting Abstract
Oncology
Gregory E. Sanda, Julie M. Shabto, Subir Goyal, Yuan Liu, Dylan J. Martini, Bassel Nazha, Jacqueline T. Brown, Lauren Beth Yantorni, Greta Russler, Sarah Caulfield, Shreyas S. Joshi, Vikram M. Narayan, Haydn Kissick, Kenneth Ogan, Viraj A. Master, Bradley Curtis Carthon, Omer Kucuk, Mehmet Asim Bilen
JOURNAL OF CLINICAL ONCOLOGY
(2022)
Article
Multidisciplinary Sciences
Masao Hashimoto, Koichi Araki, Maria A. Cardenas, Peng Li, Rohit R. Jadhav, Haydn T. Kissick, William H. Hudson, Donald J. McGuire, Rebecca C. Obeng, Andreas Wieland, Judong Lee, Daniel T. McManus, James L. Ross, Se Jin Im, Junghwa Lee, Jian-Xin Lin, Bin Hu, Erin E. West, Christopher D. Scharer, Gordon J. Freeman, Arlene H. Sharpe, Suresh S. Ramalingam, Alex Pellerin, Volker Teichgraber, William J. Greenleaf, Christian Klein, Jorg J. Goronzy, Pablo Umana, Warren J. Leonard, Kendall A. Smith, Rafi Ahmed
Summary: The study showed that combination therapy with PD-1 blockade and IL-2 during chronic lymphocytic choriomeningitis virus infection significantly alters the differentiation program of CD8(+) T cells, resulting in the generation of highly functional effector CD8(+) T cells that mediate viral control, thus providing a new perspective for cancer treatment.
Article
Multidisciplinary Sciences
Sruthi Ravindranathan, Tenzin Passang, Jian-Ming Li, Shuhua Wang, Rohan Dhamsania, Michael Brandon Ware, Mohammad Y. Zaidi, Jingru Zhu, Maria Cardenas, Yuan Liu, Sanjeev Gumber, Brian Robinson, Anish Sen-Majumdar, Hanwen Zhang, Shanmuganathan Chandrakasan, Haydn Kissick, Alan B. Frey, Susan N. Thomas, Bassel F. El-Rayes, Gregory B. Lesinski, Edmund K. Waller
Summary: By inhibiting VIP-R signaling, anti-tumor immune response in PDAC can be enhanced, leading to improved treatment efficacy and survival rates.
NATURE COMMUNICATIONS
(2022)
Article
Immunology
Nataliya Prokhnevska, Maria A. Cardenas, Rajesh M. Valanparambil, Ewelina Sobierajska, Benjamin G. Barwick, Caroline Jansen, Adriana Reyes Moon, Petra Gregorova, Luke delBalzo, Rachel Greenwald, Mehmet Asim Bilen, Mehrdad Alemozaffar, Shreyas Joshi, Cara Cimmino, Christian Larsen, Viraj Master, Martin Sanda, Haydn Kissick
Summary: Improvements in tumor immunotherapies rely on understanding the T cell response to tumors. By studying tumor-draining lymph nodes (TDLNs), it was discovered that activated CD8+ T cells in TDLNs shared characteristics with stem-like cells in tumors. These TDLN cells were revealed to be precursors of tumor-resident stem-like CD8+ T cells. Murine tumor models showed that tumor-specific CD8+ T cells were activated in TDLNs and later differentiated into effector cells in the tumor with co-stimulation.
Article
Virology
Amanda L. Gill, William H. Hudson, Rajesh M. Valanparambil, Eunseon Ahn, Donald J. McGuire, Andreas Wieland, Daniel T. McManus, Haydn T. Kissick, Rama S. Akondy, Rafi Ahmed
Summary: A better understanding of long-lived memory CD8 T cell differentiation is necessary due to increased demand for novel vaccination strategies. Using a mouse model of acute LCMV infection, we conducted an in-depth, longitudinal analysis of memory CD8 T cell subsets, examining their phenotype, transcriptional programming, and anatomical location in the spleen. We characterized a comprehensive memory phenotype associated with higher CD28 expression and found distinct localization programs within the spleen for memory subsets. These findings suggest that memory formation and survival may be influenced by location, emphasizing the importance of considering memory phenotypes and their trafficking for robust memory responses following vaccination.
JOURNAL OF VIROLOGY
(2023)
Article
Oncology
Gregory E. Sanda, Julie M. Shabto, Subir Goyal, Yuan Liu, Dylan J. Martini, Bassel Nazha, Jacqueline T. Brown, Lauren B. Yantorni, Greta Anne Russler, Sarah Caulfield, Shreyas S. Joshi, Vikram M. Narayan, Haydn Kissick, Kenneth Ogan, Viraj A. Master, Bradley C. Carthon, Omer Kucuk, Mehmet Asim Bilen
Summary: A retrospective study investigated the relationship between immune-related adverse events (irAEs) and clinical outcomes in patients with advanced urothelial cancer who received immune checkpoint inhibitor therapy. The results showed that patients with irAEs, especially dermatologic irAEs, had significantly improved overall survival (OS), progression-free survival (PFS), and clinical benefit (CB).
Meeting Abstract
Oncology
Brendan L. C. Kinney, Connor Parrish, Vikash Kansal, Zachary S. Buchwald, Haydn T. Kissick, Amy Y. Chen, Nicole C. Schmitt
Meeting Abstract
Oncology
Emily Greene, Deon Doxie, Maria Diab, Bassel El-Rayes, Shishir Maithel, Juan Sarmiento, Olatunji Alese, Jayden Kim, Cameron Herting, Kavita Dhodapkar, Madhav Dhodapkar, Haydn Kissick, Chrystal Paulos, Gregory Lesinski
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Meeting Abstract
Oncology
Caroline Jansen, Prasanthi Chappa, Nataliya Prokhnevska, Maria Cardenas, Roshan Prabhu, Jim Zhong, Kimberly Hoang, Subir Goyal, Suzanna Logan, Jeffrey Olson, Edjah Nduom, Luke del Balzo, Kirtesh Patel, Stuart Burri, Anthony Asher, Scott Wilkinson, Ross Lake, Kristin Higgins, Pretesh Patel, Vishal Dhere, Mylin Torres, Adam Sowalsky, Mohammad Khan, Haydn Kissick, Zachary Buchwald
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Meeting Abstract
Oncology
Jimmy Patel, Amber Draper, Yena Woo, Layla Dhabaan, Pretesh Patel, Ashesh Jani, Bradley Carthon, Viraj Master, Haydn Kissick, Mehmet Bilen, Zachary Buchwald, David Qian
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Meeting Abstract
Oncology
Guillermo Rangel RIvera, Connor Dwyer, Hannah Knochelmann, Aubrey Smith, Anna Cole, Megan Wyatt, Chrystal Paulos, Jessica Thaxton, Shikhar Mehrotra, Haydn Kissick, Mark Rubinstein, Gregory Lesinski
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Meeting Abstract
Oncology
Eric J. Miller, Carrie Q. Sun, Petra Gregorova, Edgars Jecs, Yesim Altas Tahirovic, Robert J. Wilson, Huy H. Nguyen, Savita K. Sharma, Perry Bartsch, Zachary Sticher, Levi Moellering, Priscilla Davidson, Ryan Jajosky, Michael D'Erasmo, Manohar Saindane, Zafer Sahin, Nicholas S. Akins, Alexander A. Kolykhalov, Lawrence Wilson, Rebecca S. Arnold, John A. Petros, Haydn Kissick, Lingjie Xu, Yi Jiang, Dennis C. Liotta
Meeting Abstract
Immunology
Nataliya Prokhnevska, Maria A. Cardenas, Rajesh Valanparambil, Ewelina Sobierajska, Caroline Jansen, Viraj Master, Martin Sanda, Haydn Kissick
JOURNAL OF IMMUNOLOGY
(2022)