Article
Immunology
Reut Levi, Yoram Louzoun
Summary: This study reveals that beta chain rearrangement in T cells is a two-step process, where D-beta and J(beta) bind first and then V-beta is joined to the complex. The frequency of V(beta)J(beta) combinations in human and mouse deviates from the expected values based on gene usage frequency. This bias is mainly observed in functional rearrangements but also slightly in non-functional rearrangements. Preferred V(beta)J(beta) combinations in functional clones are shared between donors and samples, suggesting a common structural mechanism for these biases.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Multidisciplinary Sciences
Elena R. Bovolenta, Eva M. Garcia-Cuesta, Lydia Horndler, Julia Ponomarenko, Wolfgang W. Schamel, Mario Mellado, Mario Castro, David Abia, Hisse M. van Santen
Summary: Signaling through T cell receptor (TCR) plays a critical role in the development, maintenance, and activation of T cells. This study reveals that the strength of pre-TCR-mediated signaling during T cell development determines the diversity of TCR beta repertoire for positive and negative selection.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Cell Biology
Pedro M. Rodrigues, Laura G. Sousa, Chiara Perrod, Ana R. Maceiras, Pedro Ferreirinha, Rita Pombinho, Gema Romera-Cardenas, Maria Gomez-Lazaro, Meryem Senkara, Jelena Pistolic, Didier Cabanes, Ludger Klein, Paul Saftig, Nuno L. Alves
Summary: Thymic epithelial cells (TECs) are crucial for T cell development. This study reveals that lysosomal-associated membrane protein 2 (LAMP2) is highly expressed in cortical TECs (cTECs) and plays a role in autophagy and lysosomal processes. Genetic inactivation of Lamp2 in cTECs impairs the development of CD4 T cells without directing MHC II-restricted cells into the CD8 lineage. The findings suggest that LAMP2 is important for the generation of selecting self-peptides:MHC II complexes in cTECs.
Review
Immunology
Rami Bechara, Alexia Feray, Marc Pallardy
Summary: Allergic reactions to drugs and chemicals are mediated by specific T cells and it is unclear whether there is a common occurrence of thymic selection of drug/chemical-specific T cells. Recent observations suggest that T-cell receptor recognition of hapten-modified peptides may play a crucial role in drug/chemical allergy. This understanding could lead to efficient strategies for allergy diagnosis and predicting the immunogenic potential of new chemicals.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Multidisciplinary Sciences
Sabrina Giampaolo, Cristina M. Chiarolla, Konrad Knoepper, Martin Vaeth, Matthias Klein, Azeem Muhammad, Tobias Bopp, Friederike Berberich-Siebelt, Amiya K. Patra, Edgar Serfling, Stefan Klein-Hessling
Summary: In the thymus, the deletion of NFATc1 or its inducible isoforms during the DN stages of thymocyte development leads to an increase in gamma delta thymocytes while alpha beta thymocytes are mostly unaffected. These gamma delta thymocytes upregulate PLZF, the master regulator of NKT cell development, acquiring an NKT gamma delta cell phenotype with higher survival rates. The enhancer E2 is crucial for NFATc1's suppressive function in NKT gamma delta cell formation, translating a strong gamma delta TCR signal into inducible expression of NFATc1 isoforms to control the numbers of NKT gamma delta cells.
Article
Biology
Soeun Kim, Guk-Yeol Park, Jong Seok Park, Jiho Park, Hyebeen Hong, Yoontae Lee
Summary: The transcriptional repressor Capicua (CIC) plays a critical role in controlling thymic selection process, impacting both positive and negative selection of thymocytes. CIC deficiency attenuates TCR signaling in DP cells and regulates multiple genes involved in T cell development, suggesting it serves as a safeguard against autoimmunity.
Article
Multidisciplinary Sciences
Lisa Paschold, Cornelia Gottschick, Susan Langer, Bianca Klee, Sophie Diexer, Ivona Aksentijevich, Christoph Schultheiss, Oliver Purschke, Peggy Riese, Stephanie Trittel, Roland Haase, Frank Dressler, Wolfgang Eberl, Johannes Huebner, Till Strowig, Carlos A. Guzman, Rafael Mikolajczyk, Mascha Binder
Summary: This study provides insights into the B and T cell repertoires in infants and their association with early life respiratory infections. Low antigen-dependent somatic hypermutation of B cell repertoires and low T and B cell repertoire clonality are observed at 12 months of age, reflecting immunological naivety. Infants with inadequate T cell repertoire diversity or high clonality experience more acute respiratory infections. There is no correlation between T or B cell repertoire metrics and other parameters such as sex, birth mode, siblings, pets, daycare, or breastfeeding duration.
SCIENTIFIC REPORTS
(2023)
Article
Immunology
Hao H. Yiu, Louis N. Schoettle, Marlene Garcia-Neuer, Joseph N. Blattman, Philip L. F. Johnson
Summary: This passage discusses the diversity generation of T-cell receptors in the adaptive immune system and the differences among various receptor types, focusing on the presence of public receptor sequences in different contexts and the factors influencing their abundance. Thymic or peripheral selection is identified as a significant factor in increasing the abundances of public TCR sequences.
Article
Immunology
Izumi Ohigashi, Melina Frantzeskakis, Alison Jacques, Sayumi Fujimori, Aya Ushio, Fusano Yamashita, Naozumi Ishimaru, Da Yin, Margaret Cam, Michael C. Kelly, Parirokh Awasthi, Kensuke Takada, Yousuke Takahama
Summary: The study revealed that the thymoproteasome plays a crucial role in the production of CD8(+) T cells, optimizing the cell development process. This finding indicates that the thymoproteasome regulates the formation of the TCR repertoire, playing a key role in the development of CD8(+) T cells.
JOURNAL OF EXPERIMENTAL MEDICINE
(2021)
Review
Immunology
Zahra S. Ghoreyshi, Jason T. George
Summary: TCR-pMHC interactions are crucial for immune responses, and computational methods are used to predict favorable interactions. These methods utilize protein sequence, structure, or both, and employ statistical learning-based approaches to identify specificity rules.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Immunology
Mikiya Tsunoda, Hiroyasu Aoki, Haruka Shimizu, Shigeyuki Shichino, Kouji Matsushima, Satoshi Ueha
Summary: Temporal analysis of T cell receptor (TCR) repertoire is important for monitoring changes in antigen-specific T cells in cancer patients. However, lack of experimental models for temporal analysis within a homogeneous population limits understanding of the relationship between TCR repertoire changes and antitumor responses. Bilateral tumor model showed highly similar T-cell clones in bilateral tumors and different patterns in draining lymph nodes, suggesting independent induction of tumor-reactive T cell clones in each lymph node.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Multidisciplinary Sciences
Hongyi Zhang, Xiaowei Zhan, Bo Li
Summary: The authors introduced a computationally efficient tool named GIANA for rapid clustering of millions of TCR sequences, identifying TCRs potentially associated with the response to cancer, infectious and autoimmune diseases.
NATURE COMMUNICATIONS
(2021)
Article
Ophthalmology
Xiaorui Bao, Yanlin Zhong, Chunyan Yang, Yujie Chen, Yi Han, Xiang Lin, Caihong Huang, Kejia Wang, Zuguo Liu, Cheng Li
Summary: In this study, the T-cell receptor (TCR) repertoire in the conjunctiva of a dry eye mouse model was comprehensively analyzed using flow cytometry and next-generation sequencing. The results showed unique T-cell clonotypes in the dry eye group, and these alterations were reversed after glucocorticoid treatment.
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2023)
Article
Biochemical Research Methods
Yu Zhao, Bing He, Zhimeng Xut, Yidan Zhang, Xuan Zhao, Zhi-An Huang, Fan Yang, Liang Wang, Lei Duan, Jiangning Song, Jianhua Yao
Summary: In this study, an interpretable AI model called VDJMiner was proposed to mine underlying medical conditions and predict the prognosis of COVID-19 patients based on their immune repertoires. VDJMiner accurately identified multiple medical conditions and predicted the severity of COVID-19 with high accuracy. It also provided predictions on the response to tocilizumab treatment. The results demonstrated that VDJMiner is a valuable tool for personalized treatment decision and prognosis estimation in COVID-19 patients.
BRIEFINGS IN BIOINFORMATICS
(2023)
Review
Biochemistry & Molecular Biology
Kenta Nakamura, Ryuhei Okuyama
Summary: Immune checkpoint inhibitors (ICIs) are used for the treatment of various cancers, and understanding the mechanism of tumor immune responses can improve their efficacy. Investigating T cell receptors (TCRs) and changes in the TCR repertoire has revealed increased proliferation of T cell clones in patients responding to ICIs. This proliferation is observed in tumors as well as in the peripheral blood, suggesting that analyzing immune cell repertoire can help predict and enhance the therapeutic efficacy of ICIs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Cristina Cacho-Navas, Natalia Reglero-Real, Natalia Colas-Algora, Susana Barroso, Gema de Rivas, Kostantinos Stamatakis, Jorge Feito, German Andres, Manuel Fresno, Leonor Kremer, Isabel Correas, Miguel A. Alonso, Jaime Millan
Summary: In this study, the researchers investigate the mechanisms of ICAM-1 localization and its impact on lymphocyte-hepatic epithelial cell interaction. They discover that plasmolipin plays a crucial role in ICAM-1 polarization and its absence impairs ICAM-1 transcytosis, leading to increased T-cell adhesion to hepatic epithelial cells.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Alejandro M. Hortal, Clara L. Oeste, Claudia Cifuentes, Miguel Alcoceba, Isabel Fernandez-Pisonero, Laura Clavain, Rut Tercero, Pilar Mendoza, Veronica Dominguez, Marta Garcia-Flores, Belen Pintado, David Abia, Carmen Garcia-Macias, Almudena Navarro-Bailon, Xose R. Bustelo, Marcos Gonzalez, Balbino Alarcon
Summary: The overexpression of wild type RRAS2 is found to be associated with the development of CLL. A single nucleotide polymorphism (rs8570) in the 3'UTR of RRAS2 mRNA is linked to higher expression of RRAS2 and more aggressive disease in CLL. Overexpression of wild type RRAS2 in mice provokes the development of CLL, accompanied by strong convergent selection of somatic mutations. The R-RAS2 protein physically binds to the BCR and mediates BCR signals in CLL.
Article
Oncology
Javier Galan-Martinez, Konstantinos Stamatakis, Ines Sanchez-Gomez, Silvia Vazquez-Cuesta, Nuria Girones, Manuel Fresno
Summary: TCFL5 plays an important role in the development of colorectal cancer (CRC), with its functions depending on specific isoforms. Different isoforms of TCFL5 have distinct effects on proliferation, migration, and spheroids formation in CRC cell lines. This study highlights the importance of analyzing TCFL5 isoforms separately in cancer research.
MOLECULAR ONCOLOGY
(2022)
Article
Pharmacology & Pharmacy
Konstantinos Stamatakis, Patricia Torres-Gerica, Alba Jimenez-Segovia, Edurne Ramos-Munoz, Lorena Crespo-Toro, Patricia Fuentes, Maria L. Toribio, Francisco Callejas-Hernandez, Alfredo Carrato, Maria Laura Garcia Bermejo, Manuel Fresno
Summary: COX2-regulated genes were studied in a mouse colorectal cancer cell line and circulating tumor cells (CTCs) were identified using a cell separation system. Gene expression analysis in different samples showed differences between healthy and tumor-bearing mice, which could provide valuable diagnostic and prognostic information.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Immunology
Sara Francisco, Jean-Marc Billod, Javier Merino, Carmen Punzon, Alicia Gallego, Alicia Arranz, Sonsoles Martin-Santamaria, Manuel Fresno
Summary: This study reveals that Ochrobactrum intermedium LPS can activate both TLR4 and TLR2, indicating the occurrence of TLR4/TLR2 heterodimerization, and the core saccharide plays an important role in this interaction.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Cell Biology
Isabel Fernandez-Pisonero, Laura Clavain, Javier Robles-Valero, L. Francisco Lorenzo-Martin, Ruben Caloto, Blanca Nieto, Carmen Garcia-Macias, Clara L. Oeste, Manuel Sanchez-Martin, Antonio Abad, Alejandro Hortal, Dolores Caballero, Marcos Gonzalez, Mercedes Dosil, Balbino Alarcon, Xose R. Bustelo
Summary: A missense mutation of RRAS2 (Q72L) has been identified as a hotspot mutation in cancer and Noonan syndrome, and it has been found to trigger the development of various tumors in adult tissues. These tumors show different therapeutic susceptibilities and are dependent on mTORC1 signaling. This mutation provides potential therapeutic strategies for patients with RRAS2 mutations.
Editorial Material
Respiratory System
Jose Luis Izquierdo, Clara Lillian Oeste, Ignacio Hernandez Medrano
ARCHIVOS DE BRONCONEUMOLOGIA
(2023)
Article
Biochemistry & Molecular Biology
Andres Miguel-Arribas, Ana Martin-Maria, Eef C. W. Alaerds, Jorge Val-Calvo, Luis Yuste, Fernando Rojo, David Abia, Ling Juan Wu, Wilfried J. J. Meijer
Summary: Many prokaryotic operons encode a processive antitermination (P-AT) system, but the mechanism of resistance to antitermination has not been reported until now. This study identified a conAn-resistant terminator, Ter(R), in the conjugation operon of Bacillus subtilis plasmid pLS20 and showed that its long stem is the determining feature for resistance to antitermination. This is the first reported P-AT resistance mechanism.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Immunology
Lydia Horndler, Pilar Delgado, Salvador Romero-Pinedo, Marina Quesada, Ivaylo Balabanov, Rocio Laguna-Goya, Patricia Almendro-Vazquez, Miguel A. Llamas, Manuel Fresno, Estela Paz-Artal, Hisse M. van Santen, Stela Alvarez-Fernandez, Asuncion Olmo, Balbino Alarcon
Summary: This study utilized flow cytometry to compare the efficacy of different COVID-19 vaccines in generating a protective humoral response. Significant differences were observed in the titers of anti-S antibodies produced after the first dose of the vaccines. The study also highlighted a relative reduction in antibody reactivity to the Alpha, Delta, and Kappa variants compared to the Wuhan strain after the second boosting immunization.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Oncology
Ashwathi Puravankara Menon, Beatriz Moreno, Daniel Meraviglia-Crivelli, Francesca Nonatelli, Helena Villanueva, Martin Barainka, Angelina Zheleva, Hisse M. van Santen, Fernando Pastor
Summary: CD3 complex is the first signal sensed by TCR of lymphocytes for activation, making it an attractive receptor to determine immune response fate. This article discusses the assembly of CD3-TCR complex and the approaches to harness CD3 activity for immunotherapy.
Article
Biology
Ana Martinez-Riano, Pilar Delgado, Rut Tercero, Sara Barrero, Pilar Mendoza, Clara L. L. Oeste, David Abia, Elena Rodriguez-Bovolenta, Martin Turner, Balbino Alarcon
Summary: Researchers have developed an antigen-specific in vitro germinal center system using just two cell types, B cells and CD4+ T cells, to investigate the immune response and T cell help in the production of class-switched high affinity immunoglobulins. The lack of an antigen-specific in vitro germinal center system has been a major obstacle in understanding the mechanisms of B cell:T cell cooperation. By using this system, the researchers demonstrated that T cells provide directional help to antigen-presenting B cells, but not bystander B cells, leading to the generation of class-switched antibodies.
COMMUNICATIONS BIOLOGY
(2023)
Article
Biochemical Research Methods
Ugo Bastolla, David Abia, Oscar Piette
Summary: This research explores the use of protein sequence and structure to infer evolutionary relationships. Four protein similarity measures were examined and found to be correlated, but none provided a complete and unbiased view of conservation in proteins. A new hybrid protein sequence and structure similarity score, based on the main principal component, was proposed and shown to accurately infer evolutionary divergences. A program was developed to construct protein multiple sequence alignments, achieving higher performance and similarity compared to other tools.
Article
Cardiac & Cardiovascular Systems
Ana Moya, Clara L. Oeste, Monika Beles, Sofie Verstreken, Riet Dierckx, Ward Heggermont, Jozef Bartunek, Eline Bogaerts, Imke Masuy, Dries Hens, Dario Bertolone, Marc Vanderheyden
Summary: A systematic framework based on electronic health records was developed to assess ATTR-CM patients in a real-world population of HF patients. The study found that unique combinations of cardiac and non-cardiac phenotypes, in addition to known variables, can predict ATTR-CM.
