Article
Multidisciplinary Sciences
Joseph R. R. Egan, Enas Abu-Shah, Omer Dushek, Tim Elliott, Ben D. D. MacArthur
Summary: The interaction between T cell receptors (TCRs) and peptide major histocompatibility complex (pMHC) ligands on T cells and antigen presenting cells (APCs) is often stochastic. This study reveals that the information imparted to T cells during this interaction, assessed by the entropy rate of TCR-pMHC binding dynamics, is more important than the strength of binding itself in eliciting an immune response. Optimizing the inherent stochasticity of TCR-pMHC binding dynamics may enhance effective T cell therapeutics.
JOURNAL OF THE ROYAL SOCIETY INTERFACE
(2022)
Article
Multidisciplinary Sciences
Yueyang Sun, Lu Yan, Jiajia Sun, Mingshu Xiao, Wei Lai, Guangqi Song, Li Li, Chunhai Fan, Hao Pei
Summary: Authors have developed a novel platform for identifying T cells using DNA scaffolds to organize pMHCs, allowing detection of low-affinity T cells and enhancing the binding avidity for these cells. This platform shows promise in investigating antigen-specific T cells for immune cell function or immunotherapy applications.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Xiang Zhao, Elizabeth M. Kolawole, Waipan Chan, Yinnian Feng, Xinbo Yang, Marvin H. Gee, Kevin M. Jude, Leah Sibener, Polly M. Fordyce, Ronald N. Germain, Brian D. Evavold, K. Christopher Garcia
Summary: This paper proposes a novel method to isolate TCR mutants that exhibit high activation signals coupled with low-affinity pMHC binding. Through this strategy, the mutant TCRs can enhance target killing potency while avoiding adverse cross-reactivity with off-target antigens.
Article
Biochemistry & Molecular Biology
Liang-Zhe Wu, Renu Balyan, Joanna Brzostek, Xiang Zhao, Nicholas R. J. Gascoigne
Summary: This study found that the stronger the TCR-pMHC affinity, the shorter the time required for CD8(+) T cells to commit to proliferation. The time threshold for T cell cytokine production is lower than that for cell proliferation. There is a correlation between AKT phosphorylation and T cell proliferation. The pro-inflammatory cytokine IL-15 can override the affinity-dependent features of T cell proliferation.
Article
Nanoscience & Nanotechnology
Yulin Du, Yifan Lyu, Jie Lin, Chunran Ma, Qiang Zhang, Yutong Zhang, Liping Qiu, Weihong Tan
Summary: We manipulated the intermembrane distance between antigen-presenting cells (APCs) and T cells using DNA nanostructures of different sizes. Our results show that the axial distance of the contact zone is critical for T-cell activation, likely through modulating protein reorganization and mechanical force.
NATURE NANOTECHNOLOGY
(2023)
Article
Immunology
Xiang Zhao, Liang-Zhe Wu, Esther K. Y. Ng, Kerisa W. S. Leow, Qianru Wei, Nicholas R. J. Gascoigne, Joanna Brzostek
Summary: Co-agonist pMHC class I complexes recruit CD8-bound Lck to the immune synapse to modulate CD8(+) T cell signaling pathways, enhancing effector functions and proliferation. Furthermore, co-agonism can boost T cell proliferation through an extrinsic mechanism, priming neighboring CD8(+) T cells for enhanced Akt pathway activation and proliferation.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Lukas Susac, Mai T. Vuong, Christoph Thomas, Soren von Bulow, Caitlin O'Brien-Ball, Ana Mafalda Santos, Ricardo A. Fernandes, Gerhard Hummer, Robert Tampe, Simon J. Davis
Summary: This study reveals the structure of a tumor-reactive TCR complex bound to a melanoma-specific human class I pMHC, providing insights into the initiation of TCR signaling when the receptor binds to pMHC molecules.
Article
Multidisciplinary Sciences
Rebecca C. Larson, Michael C. Kann, Stefanie R. Bailey, Nicholas J. Haradhvala, Paula Montero Llopis, Amanda A. Bouffard, Irene Scarfo, Mark B. Leick, Korneel Grauwet, Trisha R. Berger, Kai Stewart, Praju Vikas Anekal, Max Jan, Julia Joung, Andrea Schmidts, Tamara Ouspenskaia, Travis Law, Aviv Regev, Gad Getz, Marcela Maus
Summary: CAR T cell therapy has shown limited efficacy against solid tumours, and this study identifies the loss of genes in the interferon-gamma receptor signalling pathway as a potential resistance mechanism in glioblastoma and other solid tumours. The study reveals that the interferon-gamma receptor signalling pathway is critical for the adhesion and cytotoxicity of CAR T cells in solid tumours, highlighting the importance of enhancing binding interactions between T cells and tumour cells for improved responses in solid tumours.
Article
Biochemistry & Molecular Biology
Raef Shams, Yoshihiro Ito, Hideyuki Miyatake
Summary: RHEB binds to mTOR through two different binding sites, increment N-FAT-M and increment ATP, with higher affinity for increment ATP, which likely regulates the kinase activity of mTOR through multiple different binding modes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Immunology
Thomas Peacock, Benny Chain
Summary: This study compares the performance of four docking platforms in accurately modeling TCR-pMHC complexes, with HADDOCK being identified as the best performer. Docking strategy guidance is provided for obtaining the best models for future research.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Biochemistry & Molecular Biology
D. V. Shevyrev, V. P. Tereshchenko, S. V. Sennikov
Summary: The interaction between TCR and pMHC is crucial for adaptive immunity, and besides affinity, the kinetic and mechanical characteristics also play a significant role in antigen recognition and T-cell activation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Immunology
Georg Petkau, Twm J. Mitchell, Marian Jones Evans, Louise Matheson, Fiamma Salerno, Martin Turner
Summary: This article describes the role of the RNA binding protein ZFP36L1 in shaping T-cell affinity and population dynamics. ZFP36L1 promotes clonal expansion of high-affinity CD8 T cells by suppressing negative regulators of cytokine signaling and mediating a selection mechanism based on competition for IL-2.
EUROPEAN JOURNAL OF IMMUNOLOGY
(2023)
Article
Cell Biology
Lihui Wang, Xun Lan
Summary: In this study, a system called YAMTAD was designed for rapid screening of TCR-pMHC interactions. The system showed high sensitivity and specificity in identifying antigens for a given TCR and recognizing TCRs for a given pMHC. Additionally, the system demonstrated the enrichment of high-affinity TCR-pMHC interactions through library-on-library screening.
Article
Multidisciplinary Sciences
Kenji Shimizu, Daisuke Sugiura, Il-mi Okazaki, Takumi Maruhashi, Tatsuya Takemoto, Taku Okazaki
Summary: PD-1 preferentially inhibits the expression of TCR-inducible genes when TCR:pMHC affinity is low, demonstrating a qualitative control of T cell responses by suppressing low-affinity T cells. Peptide-MHC affinities and MHC expression levels do not affect PD-1 sensitivity, suggesting that the strength of individual TCR signal is the key determinant of PD-1 sensitivity.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Editorial Material
Cell Biology
Gregory M. Chen, Jan Joseph Melenhorst, Kai Tan
Summary: CAR T cell therapies targeting CD19 and CD22 have shown success in treating B cell cancers, but not in non-B cell cancers. The interaction between CAR T cells and normal B cells may play a crucial role in determining clinical CAR T cell responses.
SCIENCE TRANSLATIONAL MEDICINE
(2022)
Article
Immunology
Alexander P. R. Bally, Yan Tang, Joshua T. Lee, Benjamin G. Barwick, Ryan Martinez, Brian D. Evavold, Jeremy M. Boss
JOURNAL OF IMMUNOLOGY
(2017)
Article
Immunology
Lori Blanchfield, Joseph J. Sabatino, Laurel Lawrence, Brian D. Evavold
JOURNAL OF IMMUNOLOGY
(2017)
Article
Immunology
Rakieb Andargachew, Ryan J. Martinez, Elizabeth M. Kolawole, Brian D. Evavold
JOURNAL OF IMMUNOLOGY
(2018)
Article
Immunology
Anna Sanecka, Nagisa Yoshida, Elizabeth Motunrayo Kolawole, Harshil Patel, Brian D. Evavold, Eva-Maria Frickel
FRONTIERS IN IMMUNOLOGY
(2018)
Article
Endocrinology & Metabolism
Baoyu Liu, Jennifer D. Hood, Elizabeth M. Kolawole, Derek M. Woodruff, Dario A. Vignali, Maria Bettini, Brian D. Evavold
Article
Endocrinology & Metabolism
Maria Bettini, Marissa A. Scavuzzo, Baoyu Liu, Elizabeth Kolawole, Lin Guo, Brian D. Evavold, Malgorzata Borowiak, Matthew L. Bettini
Article
Engineering, Biomedical
Aline M. Thomas, Nicholas M. Beskid, Jennifer L. Blanchfield, Aaron M. Rosado, Andres J. Garcia, Brian D. Evavold, Julia E. Babensee
Summary: The study demonstrated that local delivery of DC10s modulates immune cell recruitment and attenuates disease progression in a preclinical model of MS.
JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A
(2021)
Article
Immunology
Heather M. Ren, Elizabeth M. Kolawole, Mingqiang Ren, Ge Jin, Colleen S. Netherby-Winslow, Quinn Wade, Shwetank, Ziaur S. M. Rahman, Brian D. Evavold, Aron E. Lukacher
SCIENCE IMMUNOLOGY
(2020)
Article
Immunology
Heejoo Kim, Jelena Perovanovic, Arvind Shakya, Zuolian Shen, Cody N. German, Andrea Ibarra, Jillian L. Jafek, Nai-Pin Lin, Brian D. Evavold, Danny H-C Chou, Peter E. Jensen, Xiao He, Dean Tantin
Summary: Loss of T cell-specific OCA-B protects mice from spontaneous autoimmune diabetes by reducing CD8(+) T cell receptor specificities associated with diabetes pathogenesis. The protective effect is recapitulated using autoantigen-specific NY8.3 mice but diminished in monoclonal models specific to artificial or neoantigens. Rational design of membrane-penetrating OCA-B peptide inhibitors normalizes glucose levels and reduces T cell infiltration and proinflammatory cytokine expression in newly diabetic NOD mice.
JOURNAL OF EXPERIMENTAL MEDICINE
(2021)
Article
Endocrinology & Metabolism
Stephen E. Gitelman, Brian N. Bundy, Ele Ferrannini, Noha Lim, J. Lori Blanchfield, Linda A. DiMeglio, Eric Felner, Jason L. Gaglia, Peter A. Gottlieb, S. Alice Long, Andrea Mari, Raghavendra G. Mirmira, Philip Raskin, Srinath Sanda, Eva Tsalikian, John M. Wentworth, Steven M. Willi, Jeffrey P. Krischer, Jeffrey A. Bluestone
Summary: Imatinib was shown to preserve beta-cell function at 12 months in patients with recent-onset type 1 diabetes, but the effect was not sustained at 24 months. Adverse events were more common in the imatinib group compared to the placebo group, with gastrointestinal issues and laboratory investigations being the most commonly reported. Further research is needed to determine the ideal dose and duration of therapy, safety and efficacy in children, and the potential of imatinib to delay or prevent progression to diabetes.
LANCET DIABETES & ENDOCRINOLOGY
(2021)
Article
Multidisciplinary Sciences
Victor Pui-Yan Ma, Yuesong Hu, Anna Kellner, Joshua M. Brockman, Arventh Velusamy, Aaron T. Blanchard, Brian D. Evavold, Ronen Alon, Khalid Salaita
Summary: T cells defend against cancer and viral infections by binding to specific peptide antigens on target cells. It has been found that the forces transmitted through the LFA-1 /ICAM-1 complex can tune T cell signaling and enhance T cell activation and TCR discrimination.
Article
Immunology
Nguyen X. Nguyen, Andrew W. Richens, Linda M. Sircy, Denise E. Allard, Elizabeth M. Kolawole, Brian D. Evavold, Maria Bettini, J. Scott Hale
Summary: The AIM assay is a cytokine-independent technique for identifying Ag-specific T cells based on upregulated expression of activation markers after Ag restimulation. This study analyzed immune responses of TCR-transgenic CD4+ T cells and found that the AIM assay is effective for identifying the frequency of protein immunization-induced effector and memory CD4+ T cells but has limitations in identifying cells induced by viral infection, especially chronic infection. The findings suggest that the AIM assay is a useful tool for quantifying murine Ag-specific CD4+ T cells in protein vaccination.
JOURNAL OF IMMUNOLOGY
(2023)
Article
Engineering, Biomedical
Aaron M. Rosado, Yan Zhang, Hyun-Kyu Choi, Yunfeng Chen, Samuel M. Ehrlich, Fengzhi Jin, Arash Grakoui, Brian D. Evavold, Cheng Zhu
Summary: Protein-protein interactions play a crucial role in coordinating biological processes and can affect an organism's responses to changing environments and diseases. In this study, we discuss memory effects in repetitive protein-protein interactions and propose several mathematical models for quantitatively analyzing these effects. We found that interactions between cell membrane proteins and peptide-major histocompatibility complex exhibit short-term memory, while peptide dissociation from MHC results in intermediate- and long-term memories. This research provides valuable insights into the mechanisms of protein interactions and can aid future studies.
APL BIOENGINEERING
(2023)
Correction
Oncology
Tamson Moore, Courtney Regan Wagner, Gina M. Scurti, Kelli A. Hutchens, Constantine Godellas, Ann Lau Clark, Elizabeth Motunrayo Kolawole, Lance M. Hellman, Nishant K. Singh, Fernando A. Huyke, Siao-Yi Wang, Kelly M. Calabrese, Heather D. Embree, Rimas Orentas, Keisuke Shirai, Emilia Dellacecca, Elizabeth Garrett-Mayer, Mingli Li, Jonathan M. Eby, Patrick J. Stiff, Brian D. Evavold, Brian M. Baker, I. Caroline Le Poole, Boro Dropulic, Joseph I. Clark, Michael I. Nishimura
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2018)
Article
Oncology
Tamson Moore, Courtney Regan Wagner, Gina M. Scurti, Kelli A. Hutchens, Constantine Godellas, Ann Lau Clark, Elizabeth Motunrayo Kolawole, Lance M. Hellman, Nishant K. Singh, Fernando A. Huyke, Siao-Yi Wang, Kelly M. Calabrese, Heather D. Embree, Rimas Orentas, Keisuke Shirai, Emilia Dellacecca, Elizabeth Garrett-Mayer, Mingli Li, Jonathan M. Eby, Patrick J. Stiff, Brian D. Evavold, Brian M. Baker, I. Caroline Le Poole, Boro Dropulic, Joseph I. Clark, Michael I. Nishimura
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2018)