Article
Immunology
Philipp Lueckemeier, Katherine L. Molter, Sebastian Jarosch, Patrick Huppertz, Anna Purcarea, Manuel J. P. Effenberger, Magdalena Nauerth, Elvira D'Ippolito, Kilian Schober, Dirk H. Busch
Summary: The avidity of TCRs plays a crucial role in T cell response to antigens, and low and high avidity T cells have distinct functions in different phases of immune responses. By inducing polyclonal T cell responses and investigating TCR-pMHC k(off)-rates, the global avidity of physiological polyclonal populations can be accurately assessed. Global k(off)-rates provide a reliable measure of the functionality of polyclonal T cell populations and are essential for evaluating polyclonal immune responses and designing polyclonal T cell therapeutics.
EUROPEAN JOURNAL OF IMMUNOLOGY
(2022)
Article
Multidisciplinary Sciences
Kimberly G. Laffey, Robert J. Stiles, Melissa J. Ludescher, Tessa R. Davis, Shariq S. Khwaja, Richard J. Bram, Peter J. Wettstein, Venkataraman Ramachandran, Christopher A. Parks, Edwin E. Reyes, Alejandro Ferrer, Jenna M. Canfield, Cory E. Johnson, Richard D. Hammer, Diana Gil, Adam G. Schrum
Summary: During normal T cell development, a low-frequency population of early all TCR+ DN cells is present, which requires CD3δ for their generation/detection. These cells can respond to MHC and display coreceptor-independent MHC reactivity. It has been observed that these cells are susceptible to T-ALL transformation.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Review
Immunology
Connie B. Gilfillan, Michael Hebeisen, Nathalie Rufer, Daniel E. Speiser
Summary: The functional avidity (FA) of cytotoxic CD8 T cells plays a crucial role in their functional capabilities and protection from infection and cancer. The factors influencing FA and its regulation mechanisms are still not fully understood, but recent research suggests that FA may be stable in vivo due to continued signaling modulation.
EUROPEAN JOURNAL OF IMMUNOLOGY
(2021)
Review
Immunology
Roy A. Mariuzza, Daichao Wu, Brian G. Pierce
Summary: This review summarizes recent studies on the structural and biophysical aspects of T cell receptor (TCR) recognition of shared cancer neoantigens derived from oncogenes. The findings reveal the correlation between different mutations and the antigen presentation, and discuss the potential of TCR-mimic antibodies as an alternative to TCRs for targeting cancer neoantigens. Additionally, the review highlights recent computational advances and the significance of structural information in predicting neoepitope immunogenicity.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Jun Chang
Summary: The MHC multimer technology has revolutionized the quantification and analysis of antigen-specific T cells, especially CD8 T cells. Its application has expanded to various T cell types and functions, including cell sorting and single-cell classification through DNA barcodes.
MOLECULES AND CELLS
(2021)
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.
Review
Immunology
Maki Nakayama, Aaron W. Michels
Summary: TCRs serve as unique markers that define antigen specificity for T cells, making them prime candidates for next-generation T cell biomarkers. Developing TCR biomarkers for T1D could potentially provide powerful tools for assessing disease activity and treatment development in diabetes.
FRONTIERS IN IMMUNOLOGY
(2021)
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
Immunology
Even Walseng, Bo Wang, Chunning Yang, Pooja Patel, Chihao Zhao, Hanzhi Zhang, Peng Zhao, Yariv Mazor
Summary: T cell engagers, a type of immunotherapy, face challenges in targeting low density tumor-specific antigens. This study demonstrates the importance of design parameters for developing T cell engagers that can efficiently target these antigens.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Oncology
My Thi Viet Ha, Hiroshi Hamana, Kiyomi Shitaoka, Abdul Hayee, Eiji Kobayashi, Toshiaki Yoshikawa, Tetsuya Nakatsura, Reiko Saikawa, Eri Sato, Mitsujiro Osawa, Yasumichi Hitoshi, Tung Son Dang, Tatsuhiko Ozawa, Hiroyuki Kishi
Summary: This study attempted to establish a simple method to select high-functional TCRs based on the expression of T cell activation markers. The expression levels of CD69, CD137, and PD-1 were found to be associated with high-functional TCRs. This method will promote the development of TCR-T cell therapy.
Article
Immunology
Dmitrii S. Shcherbinin, Vadim K. Karnaukhov, Ivan V. Zvyagin, Dmitriy M. Chudakov, Mikhail Shugay
Summary: This study aims to extend and analyze the available structures of TCR-peptide-MHC complexes using highly accurate template-based modeling, providing a methodology to predict TCR specificity.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Immunology
Yang Wang, Alexandra Tsitsiklis, Stephanie Devoe, Wei Gao, H. Hamlet Chu, Yan Zhang, Wei Li, Wing Ki Wong, Charlotte M. Deane, David Neau, Jill E. Slansky, Paul G. Thomas, Ellen A. Robey, Shaodong Dai
Summary: Certain CD8 T cell responses, such as those found in individuals harboring HLA-B57 and controlling HIV infection, are highly effective. A study focused on a protective CD8 T cell response against a parasite-derived peptide called HF10 found that this response is characterized by a specific T cell receptor (TCR) repertoire dominated by V beta 2. The study also revealed an unusual structure of the TCR in complex with the peptide-presenting molecule (MHC), with both MHC and TCR contributing extensively to peptide specificity and leaving a parallel footprint on the TCR's pMHC ligand. These findings suggest that V beta 2 and the molecule H-2Ld may play specialized roles in antigen recognition, leading to strong and focused T cell responses.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Multidisciplinary Sciences
Ke Pan, Yulun Chiu, Eric Huang, Michelle Chen, Junmei Wang, Ivy Lai, Shailbala Singh, Rebecca M. Shaw, Michael J. MacCoss, Cassian Yee
Summary: T cell responses are crucial for recovery and immune protection from SARS-CoV-2 infections, with epitopes best defined by analyzing peptides eluted from the naturally processed peptide-MHC. Traditional in silico methods for predicting immunogenic epitopes may not always be effective in eliciting T cell responses, highlighting the importance of empirical analysis for identifying immunogenic epitopes. T cell receptor-engineered T cell technology for targeting and killing SARS-CoV-2 target cells is currently unavailable, but mass spectrometric analysis of MHC-eluted peptides shows promise in identifying immunogenic epitopes and enabling engineered TCR-redirected killing.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biochemical Research Methods
Shirit Dvorkin, Reut Levi, Yoram Louzoun
Summary: The study introduces an autoencoder named ELATE to represent T cell receptors as real vectors for characterizing donors and specific receptors. By combining distance conserving autoencoders and Kernel Density Estimates, local repertoire density can be estimated to study repertoire properties.
PLOS COMPUTATIONAL BIOLOGY
(2021)
Article
Immunology
Lihua Deng, Cedric Ly, Sina Abdollahi, Yu Zhao, Immo Prinz, Stefan Bonn
Summary: This study provides a general method for collecting and preprocessing TCR-pMHC binding data and generates comprehensive datasets for comparing prediction models. The performance evaluation of five deep learning models reveals that they have limitations in generalization and robustness. These findings suggest that TCR-pMHC binding prediction remains challenging and requires further improvement in data quality and algorithmic approaches.
FRONTIERS IN IMMUNOLOGY
(2023)
