Methods for sequence and structural analysis of B and T cell receptor repertoires

Teraguchi, Shunsuke; Saputri, Dianita S.; Llamas-Covarrubias, Mara Anaís; Davila, Ana; Díez, Diego; Nazlica, Sedat Aybars; Rozewicki, John; Ismanto, Hendra S.; Wilamowski, Jan; Xie, Jiaqi; Xu, Zichang; Loza-Lopez, Martin de Jesus; Eerden, Floris J. van; Li, Songling; Standley, Daron M.

doi:10.1016/j.csbj.2020.07.008

Cited by 28 publications

(22 citation statements)

References 136 publications

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“…In addition to immune-cell phenotyping using multiparameter cytometry (flow or mass) and immunoproteomics, gene expression is widely used to identify signatures and predictors of vaccine-induced specific antibody and T-cell responses. Furthermore, transcriptomic and genomic data (using next-generation sequencing) allow to capture the diversity of the immune repertoire induced by vaccines [80], with a comprehensive quantification of full-length T cell receptor (TCR) and B cell receptor (BCR) variable region sequences [81]. Additional layers of information, including epigenomic (using ChIP-Seq or ATAC-Seq), metabolomic (using nuclear magnetic resonance spectroscopy and mass spectrometry), and that from the microbiome (using 16S rRNA or shotgun metagenomic sequencing) can be used to further characterize vaccine responses, as appropriate technologies are becoming available [38,82].…”

Section: Omics Technologiesmentioning

confidence: 99%

Predictive Markers of Immunogenicity and Efficacy for Human Vaccines

et al. 2021

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Vaccines represent one of the major advances of modern medicine. Despite the many successes of vaccination, continuous efforts to design new vaccines are needed to fight “old” pandemics, such as tuberculosis and malaria, as well as emerging pathogens, such as Zika virus and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Vaccination aims at reaching sterilizing immunity, however assessing vaccine efficacy is still challenging and underscores the need for a better understanding of immune protective responses. Identifying reliable predictive markers of immunogenicity can help to select and develop promising vaccine candidates during early preclinical studies and can lead to improved, personalized, vaccination strategies. A systems biology approach is increasingly being adopted to address these major challenges using multiple high-dimensional technologies combined with in silico models. Although the goal is to develop predictive models of vaccine efficacy in humans, applying this approach to animal models empowers basic and translational vaccine research. In this review, we provide an overview of vaccine immune signatures in preclinical models, as well as in target human populations. We also discuss high-throughput technologies used to probe vaccine-induced responses, along with data analysis and computational methodologies applied to the predictive modeling of vaccine efficacy.

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Section: Omics Technologiesmentioning

confidence: 99%

Predictive Markers of Immunogenicity and Efficacy for Human Vaccines

et al. 2021

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“…As more structures for more diverse epitopes and TCRs become available, we expect that both homology modelling accuracy and performance of the classifier will improve. Structure-prediction is now a fast-moving field and we might soon be able to apply newer and improved methods to the TCR-pMHC prediction problem, able to account for the highly diverse CDR loops (Teraguchi et al, 2020 ). Compared to other tools, TCRpMHCmodels is attractive in its ability to produce a quick prediction of the entire TCR-pMHC complex, without relying on docking methods, which still need to be optimised for this task (Peacock and Chain, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Predicting T Cell Receptor Antigen Specificity From Structural Features Derived From Homology Models of Receptor-Peptide-Major Histocompatibility Complexes

2021

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The physical interaction between the T cell receptor (TCR) and its cognate antigen causes T cells to activate and participate in the immune response. Understanding this physical interaction is important in predicting TCR binding to a target epitope, as well as potential cross-reactivity. Here, we propose a way of collecting informative features of the binding interface from homology models of T cell receptor-peptide-major histocompatibility complex (TCR-pMHC) complexes. The information collected from these structures is sufficient to discriminate binding from non-binding TCR-pMHC pairs in multiple independent datasets. The classifier is limited by the number of crystal structures available for the homology modelling and by the size of the training set. However, the classifier shows comparable performance to sequence-based classifiers requiring much larger training sets.

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“…Finally, we wish to highlight that this in vivo approach could help to identify new peptide-specific TCR sequences and confirm already established datasets ( Teraguchi et al, 2020 ). Even though TCR datasets are growing, the number of TCRs with known Ag specificity and function is extremely low ( Shugay et al, 2018 ; Zvyagin et al, 2020 ).…”

Section: Discussionmentioning

confidence: 57%

Receptor repertoires of murine follicular T helper cells reveal a high clonal overlap in separate lymph nodes in autoimmunity

Niebuhr

Belde

Fähnrich

et al. 2021

eLife

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Follicular T helper cells (Tfh) are a specialized subset of CD4 effector T cells that are crucial for germinal center (GC) reactions and for selecting B cells to undergo affinity maturation. Despite this central role for humoral immunity, only few data exist about their clonal distribution when multiple lymphoid organs are exposed to the same antigen (Ag) as it is the case in autoimmunity. Here, we used an autoantibody-mediated disease model of the skin and injected one auto-Ag into the two footpads of the same mouse and analyzed the T cell receptor (TCR)β sequences of Tfh located in GCs of both contralateral draining lymph nodes. We found that over 90% of the dominant GC-Tfh clonotypes were shared in both lymph nodes but only transiently. The initially dominant Tfh clonotypes especially declined after establishment of chronic disease while GC reaction and autoimmune disease continued. Our data demonstrates a dynamic behavior of Tfh clonotypes under autoimmune conditions and emphasizes the importance of the time point for distinguishing auto-Ag-specific Tfh clonotypes from potential bystander activated ones.

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Methods for sequence and structural analysis of B and T cell receptor repertoires

Abstract: Graphical abstract

Cited by 28 publications

References 136 publications

Predictive Markers of Immunogenicity and Efficacy for Human Vaccines

Predictive Markers of Immunogenicity and Efficacy for Human Vaccines

Predicting T Cell Receptor Antigen Specificity From Structural Features Derived From Homology Models of Receptor-Peptide-Major Histocompatibility Complexes

Receptor repertoires of murine follicular T helper cells reveal a high clonal overlap in separate lymph nodes in autoimmunity

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