Article
Cell Biology
Adi Nagler, Shelly Kalaora, Chaya Barbolin, Anastasia Gangaev, Steven L. C. Ketelaars, Michal Alon, Joy Pai, Gil Benedek, Yfat Yahalom-Ronen, Noam Erez, Polina Greenberg, Gal Yagel, Aviyah Peri, Yishai Levin, Ansuman T. Satpathy, Erez Bar-Haim, Nir Paran, Pia Kvistborg, Yardena Samuels
Summary: This study identified SARS-CoV-2-derived peptides presented by HLA-I and HLA-II molecules, some of which are immunogenic, potentially aiding in the development of next-generation SARS-CoV-2 vaccines.
Article
Genetics & Heredity
Jana Sticht, Miguel Alvaro-Benito, Stefan Konigorski
Summary: Type 1 diabetes is an autoimmune disease with increasing incidence in high-income countries. Genetic and environmental factors play important roles in its pathogenesis. A comprehensive genetic association analysis of the HLA region can provide deeper insights into the etiology of the disease.
FRONTIERS IN GENETICS
(2021)
Article
Cell Biology
Yuan Chen, Georgina H. Mason, D. Oliver Scourfield, Alexander Greenshields-Watson, Tracey A. Haigh, Andrew K. Sewell, Heather M. Long, Awen M. Gallimore, Pierre Rizkallah, Bruce J. MacLachlan, Andrew Godkin
Summary: CD4+ T cells recognize a diverse range of SARS-CoV-2 peptide epitopes, contributing to immune memory and limiting COVID-19 disease. The immunogenicity of these peptides does not correlate with their binding affinity to HLA-DR1. X-ray crystallographic structures of six epitopes bound to HLA-DR1 reveal the molecular impact of viral variant mutations on epitope presentation. Omicron variant escapes immune recognition through mutations in TCR-facing epitope positions and a single amino acid substitution that alters the peptide-HLA structure.
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
Endocrinology & Metabolism
Elizabeth K. M. Johnstone, Mohammed Akli Ayoub, Rebecca J. Hertzman, Heng B. See, Rekhati S. Abhayawardana, Ruth M. Seeber, Kevin D. G. Pfleger
Summary: This study investigated the heteromerization of AT(2) and B-2 receptors in HEK293FT cells. The results demonstrated the functional interaction between these receptors and the differences in signaling, providing important evidence for studying GPCR pharmacology and signaling diversity.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Immunology
Beibei Wu, Arunachalam Ramaiah, Gustavo Garcia, Spyridon Hasiakos, Vaithilingaraja Arumugaswami, Sonal Srikanth
Summary: This study revealed the different effects of ORAI1 and STIM1 on SARS-CoV-2 infection. Knockout of STIM1 resulted in enhanced resistance to viral infection, while ORAI1 deletion increased susceptibility. ORAI1-mediated Ca2+ signaling played an important role in regulating baseline IFN-I levels, determining host resistance to SARS-CoV-2 infection.
JOURNAL OF IMMUNOLOGY
(2022)
Article
Immunology
Carlos A. Brito-Sierra, Megan B. Lannan, Robert W. Siegel, Laurent P. Malherbe
Summary: Using MHC-associated peptide proteomics, researchers identified the HLA-DR and HLA-DQ immunopeptidomes of three different AAV serotypes, revealing multiple promiscuous peptides with cross-reactivity. Despite high sequence homology, there were few identical peptides among the immunopeptidomes of AAV2, AAV6, and AAV9.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Microbiology
Wakako Furuyama, Kyle Shifflett, Heinz Feldmann, Andrea Marzi
Summary: EBOV sGP plays a dual role in enhancing viral infectivity by promoting virus uptake in endosomes and activating the MAPK signaling pathway for increased replication. In a mouse model, sGP treatment significantly increases virus titers in the liver, suggesting its potential as a therapeutic target for EBOV.
Article
Chemistry, Multidisciplinary
Kohei Tsuji, Kofi Baffour-Awuah Owusu, Yutaro Miura, Takahiro Ishii, Kouki Shinohara, Takuya Kobayakawa, Akino Emi, Takashi Nakano, Youichi Suzuki, Hirokazu Tamamura
Summary: Membrane fusion is a crucial step in the replication cycles of SARS-CoV-2 and HIV-1. Researchers have developed potent fusion inhibitors for SARS-CoV-2 and HIV-1 based on specific peptide sequences. This study reports the development of dimerized HR2 peptides for SARS-CoV-2, which exhibit significantly higher antiviral activity compared to monomers, suggesting a potential strategy for designing effective inhibitors for SARS-CoV-2.
Article
Immunology
Qi Ai, Fanlu Li, Siyi Zou, Zehui Zhang, Yangbing Jin, Lingxi Jiang, Hao Chen, Xiaxing Deng, Chenghong Peng, Nan Mou, Chenlei Wen, Baiyong Shen, Qian Zhan
Summary: KRAS(G12V) mutation is a driving factor of solid tumors, and TCR-engineered CD4(+) T cells specific to KRAS(G12V) demonstrate significant efficacy in vitro and in vivo, targeting APCs presenting the mutation peptide.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Cell Biology
Robert Parker, Thomas Partridge, Catherine Wormald, Rebeca Kawahara, Victoria Stalls, Maria Aggelakopoulou, Jimmy Parker, Rebecca Powell Doherty, Yoanna Ariosa Morejon, Esther Lee, Kevin Saunders, Barton F. Haynes, Priyamvada Acharya, Morten Thaysen-Andersen, Persephone Borrow, Nicola Ternette
Summary: This study profiles the repertoire of HLA-DR-bound peptides presented by monocyte-derived dendritic cells pulsed with SARS-CoV-2 spike protein. It identifies 209 unique peptide sequences mapping to various sites on the S protein, with substantial trimming of glycan residues observed on the bound peptides. The study also highlights the receptor-binding motif in S1 as a HLA-DR-binding peptide-rich region and identifies potential target peptides in S2 for cross-protective vaccine-elicited responses.
Article
Endocrinology & Metabolism
Estefania Quesada-Masachs, Samuel Zilberman, Sakthi Rajendran, Tiffany Chu, Sara McArdle, William B. Kiosses, Jae-Hyun M. Lee, Burcak Yesildag, Mehdi A. Benkahla, Agnieszka Pawlowska, Madeleine Graef, Susanne Pfeiffer, Zbigniew Mikulski, Matthias von Herrath
Summary: This study characterized and quantified the expression of HLA class II in human pancreatic tissue, showing that HLA-II can be expressed by pancreatic beta cells from patients with type 1 diabetes. It also demonstrated that this upregulation can be induced in vitro in healthy isolated human islets or reaggregated human islets by treatment with proinflammatory cytokines. The findings support a role for HLA-II in type 1 diabetes pathogenesis as potential targets for autoreactive CD4(+) lymphocytes.
Article
Immunology
Juan Francisco Gutierrez-Bautista, Antonio Sampedro, Esther Gomez-Vicente, Javier Rodriguez-Granger, Juan Antonio Reguera, Fernando Cobo, Francisco Ruiz-Cabello, Miguel Angel Lopez-Nevot
Summary: This study investigates the association between HLA-Class II typing and the intensity of humoral response to the SARS-CoV2 mRNA 1273 vaccine. The findings suggest a possible relationship between HLA-DRB1*07:01 allele and HLA-DRB1*07:01 similar to DQA1*02:01 similar to DQB1*02:02 haplotype with higher antibody production 30 days after the administration of the second dose of mRNA-1273.
Article
Medicine, Research & Experimental
Rebecca A. Porritt, Lisa Paschold, Magali Noval Rivas, Mary Hongying Cheng, Lael M. Yonker, Harsha Chandnani, Merrick Lopez, Donjete Simnica, Christoph Schultheiss, Chintda Santiskulvong, Jennifer Van Eyk, John K. McCormick, Alessio Fasano, Ivet Bahar, Mascha Binder, Moshe Arditi
Summary: Our study found a significant expansion of TCR beta variable gene 11-2 (TRBV11-2) in MIS-C patients, with extensive junctional diversity observed in the expanded TRBV11-2 clones. This expansion was correlated with the severity of MIS-C and serum cytokine levels, suggesting a novel mechanism of T cell expansion independent of CDR3. Additionally, in silico modeling indicated a potential interaction between the V beta chain encoded by TRBV11-2 and the superantigen-like motif of SARS-CoV-2 spike glycoprotein, possibly mediating T cell expansion and activation in MIS-C patients.
JOURNAL OF CLINICAL INVESTIGATION
(2021)
Article
Immunology
Mark N. Lee, Matthew Meyerson
Summary: This study introduces a high-throughput epitope identification system that combines T cell-secreted cytokines capture, cell sorting, and next-generation sequencing to identify new class I- and class II-restricted epitopes. The technology successfully validated known viral, neoepitope, and autoimmune epitope-specific TCR targets, as well as discovered new epitopes encoded by the human cytomegalovirus genome. This cytokine capture-based assay enables pooled screening of thousands of encoded peptides for epitope discovery and may lead to identification of HLA-epitope-TCR complexes relevant to disease control, etiology, or treatment.
SCIENCE IMMUNOLOGY
(2021)
