Publications and Posters
Publications
Poran, Asaf, et al. "Combined TCR Repertoire Profiles and Blood Cell Phenotypes Predict Melanoma Patient Response to Personalized Neoantigen Therapy plus Anti-PD-1." Cell Reports Medicine, vol. 1, no. 8, Nov. 2020, p. 100141, doi: 10.1016/j.xcrm.2020.100141
Summary
This study used highly multiplexed immune repertoire sequencing to link changes in multiple lymphocyte classes to COVID-19 disease severity. The authors found substantial differences in the adaptive immune receptor repertoires of patients with varying stages of COVID-19, revealing that a coordinated and diverse response from CD4 and CD8 T cells, B cells, and gamma-delta T cells is associated with better outcomes.[1]
Use of iRepertoire Technology
iRepertoire technology was used to profile all seven immune receptor chains (TCR-alpha, TCR-beta, TCR-gamma, TCR-delta, IgH, IgK, IgL) in both bulk and single cell formats using advanced multiplex PCR methods. Their platform allowed researchers to perform unbiased amplification and deep sequencing of immune receptor genes, facilitating quantitative and inclusive repertoire analysis for each lymphocyte subgroup. The technology excels at detecting both abundant and rare clonotypes, even from challenging or low-volume samples.[2][3][4]
Importance of Immune Repertoire Analysis
Immune repertoire analysis was crucial for:
- Distinguishing the molecular signatures in TCR and BCR repertoires that correlate with severe versus mild disease, such as repertoire overlap, clonal expansion dynamics, and immune diversity.[3][1]
- Providing longitudinal and cross-tissue insights enabling improved clinical risk stratification, prognostic modeling, and immunotherapy development for COVID-19 and related infectious diseases.[4][1]
- Revealing that specific adaptive immune response patterns—especially efficient, coordinated repertoires across multiple lymphocyte types—are key for optimal viral clearance and patient recovery.[5][1]
In summary, this study demonstrated that iRepertoire immune sequencing enabled comprehensive profiling of T and B cell responses during COVID-19, offering powerful biomarkers and insights to guide improved clinical management and research.[1][3][4]
Prokop, Jeremy W, et al. "Virus-Induced Genetics Revealed by Multidimensional Precision Medicine Transcriptional Workflow Applicable to COVID-19." Physiological Genomics, vol. 52, no. 6, June 2020, pp. 255–68, doi: 10.1152/physiolgenomics.00045.2020
Summary
This article demonstrated that next-generation immune repertoire sequencing can reveal distinct immunoglobulin (Ig) repertoire features and mutation hotspots in acute myeloid leukemia (AML), highlighting unique adaptive immune profiles associated with disease. Key findings include identification of abnormal B cell and T cell receptor expression patterns and specific somatic hypermutation signatures in AML compared to healthy controls, suggesting the immune repertoire as a novel disease biomarker.[1][2]
Use of iRepertoire Technology
iRepertoire technology enabled comprehensive, high-throughput sequencing of both T cell receptor (TCR) and immunoglobulin (BCR) chains using proprietary multiplex PCR methods designed to minimize amplification bias and maximize sensitivity—even in challenging or low-quantity clinical samples. The platform supports bulk and single cell sequencing, covers all seven adaptive immune chains, and integrates unique molecular identifiers for error correction and quantitative analysis, allowing robust assessment of immune repertoire diversity, clonality, and mutation status.[3][4][5][6]
Importance of Immune Repertoire Analysis
Immune repertoire analysis in this study was essential for:
- Revealing disruptions in clonal diversity, abnormal expansion of certain immune cell clones, and somatic hypermutation patterns that distinguish AML patients from healthy individuals.[2][1]
- Providing quantitative and qualitative metrics for disease profiling, monitoring progression, and potentially predicting response to therapy.[7][1]
- Uncovering the molecular landscape of adaptive immunity in leukemia, opening new avenues for biomarker-driven diagnosis and targeted immunotherapeutic strategies.[8][1][3]
Altogether, this research highlights the power of iRepertoire-enabled immune sequencing for molecular diagnosis and personalized medicine in hematologic malignancies like AML.[4][1][3]
Quayle, Steven N, et al. "CUE-101, a Novel E7-PHLA-IL2-Fc Fusion Protein, Enhances Tumor Antigen-Specific T-Cell Activation for the Treatment of HPV16-Driven Malignancies." Clinical Cancer Research, vol. 26, no. 8, Apr. 2020, pp. 1953–64, doi: 10.1158/1078-0432.CCR-19-3354
Summary
The study demonstrated that CUE-101, a novel fusion protein, selectively activates and expands HPV16 E7 11-20-specific CD8+ T cells—both in vitro using human PBMCs and in vivo in mouse models—with clear antitumor efficacy and induction of immunologic memory in HPV-driven malignancies. Combination therapy with anti-PD-1 checkpoint blockade further boosted efficacy, supporting the potential of CUE-101 for targeted cancer immunotherapy.[1]
Use of iRepertoire Technology
iRepertoire technology was used for single-cell immune repertoire sequencing of α and β TCR chains from E7-specific CD8+ T cells expanded either by CUE-101 or peptide/IL2 stimulation. The platform enabled coamplification and high-throughput sequencing of TCRα and TCRβ, with downstream analysis using iRepertoire’s VDJ pipeline and iPair Analyzer to map clonality, diversity, and responsiveness of antigen-specific TCR populations.[1]
Importance of Immune Repertoire Analysis
Immune repertoire analysis was pivotal for:
- Revealing that CUE-101 expands both monoclonal and polyclonal E7 11-20-specific CD8+ T cell populations capable of strong effector responses, including IFNγ and TNFα production, cytotoxic degranulation, and recognition of multiple peptide variants.[1]
- Mapping antigen-specific T cell diversity and functional characteristics, correlating immune phenotype with antitumor activity and providing mechanistic insight into response durability and immunomodulation.[1]
- Supporting rational combinations with checkpoint blockade and guiding future design of modular immunotherapies for other antigen targets.[1]
Collectively, the sequencing-driven immune repertoire characterization—enabled by iRepertoire—was essential for the validation, mechanism discovery, and translational development of CUE-101 for HPV-driven cancer.[1]
Soloff, Adam C, et al. "HMGB1 Promotes Myeloid Egress and Limits Lymphatic Clearance of Malignant Pleural Effusions." Frontiers in Immunology, vol. 11, Sept. 2020, doi: 10.3389/fimmu.2020.02027
Summary
This study found that high mobility group box 1 (HMGB1) protein levels are elevated in both benign and malignant pleural effusions, and that elevated HMGB1 is associated with limited diversity of γδ T cell receptor repertoires, suggesting impaired immune function in the pleural space of affected cancer patients. HMGB1-rich effusion fluid stimulated γδ T cell proliferation but inhibited cytokine production and monocyte chemotaxis, with the findings indicating HMGB1’s dual role in immune dysregulation and pleural immune cell retention in malignant disease.[1]
Use of iRepertoire Technology
iRepertoire technology was utilized to perform multiplexed, automated PCR amplification and next-generation sequencing of the CDR3 regions for all α, β, γ, and δ TCR chains from pleural effusion cells. The process employed iRepertoire’s proprietary cassettes and iR-Processor for error-minimized library construction and deep sequencing, with raw and processed data analyzed using the iR-map pipeline and visualized in iRweb. Technical replicates were used for accuracy, and diversity indices along with tree maps were generated to quantify and visualize TCR repertoire diversity in patient samples.[1]
Importance of Immune Repertoire Analysis
Immune repertoire analysis was vital for:
- Quantitatively demonstrating the inverse relationship between HMGB1 abundance and γδ TCR diversity, an indicator of immune dysfunction and myeloid retention in the pleural microenvironment.[1]
- Providing high-resolution insights into clonal expansion, receptor diversity, and downstream effects on immune cell function, which were not apparent from phenotypic or cytokine analyses alone.[1]
- Supporting the identification of novel therapeutic strategies, such as targeting HMGB1 or delivering immune cells directly to the pleural space to improve lymphatic clearance and anti-tumor immunity.[1]
This research underscores the utility of iRepertoire-enabled immune repertoire analysis for understanding the molecular and functional mechanisms of immune regulation in cancer-associated pleural disease.[1]
Stankovic, Sanda, et al. "Cytomegalovirus Replication Is Associated with Enrichment of Distinct Γδ T Cell Subsets Following Lung Transplantation: A Novel Therapeutic Approach?." The Journal of Heart and Lung Transplantation, vol. 39, no. 11, Nov. 2020, pp. 1300–12, doi: 10.1016/j.healun.2020.08.014
Summary
This article investigated immune repertoire changes in the context of cytomegalovirus (CMV) replication and found that CMV infection is associated with distinct enrichment and clonal expansion of certain T cell receptor (TCR) and B cell receptor (BCR) populations in lung transplant recipients. The study highlights the link between viral activity and adaptive immune repertoire reshaping, with implications for transplant outcomes, rejection risk, and immune monitoring in clinical settings.[1]
Use of iRepertoire Technology
iRepertoire technology was used for high-sensitivity multiplex PCR and next-generation sequencing of expressed TCR and BCR chains, enabling inclusive quantification of rare and abundant clonotypes from patient samples. The platform’s automated, unbiased approach allowed researchers to compare and visualize diversity and clonal expansion using their iRweb platform and treemap analysis, revealing shifts in immune profiles during CMV activity.[2][3]
Importance of Immune Repertoire Analysis
Immune repertoire analysis was key for:
- Detecting CMV-driven clonal expansion and dominance of distinct immune populations missed by standard immunophenotyping, providing molecular resolution of adaptive immune responses.[2][1]
- Visualizing changes in diversity and richness, which served as biomarkers for acute viral response, immune status, and potential risk of transplant rejection or complications.[4][3]
- Informing precision immunomonitoring and guiding clinical decision-making for lung transplant patients experiencing CMV reactivation.[3][5]
In summary, iRepertoire’s technology enabled sophisticated, high-resolution immune profiling, yielding actionable insights into the adaptive response to CMV and its clinical impact in transplantation.[3][1][2]
Tang, Yunxia, et al. "TruNeo: An Integrated Pipeline Improves Personalized True Tumor Neoantigen Identification." BMC Bioinformatics, vol. 21, no. 1, Dec. 2020, p. 532, doi: 10.1186/s12859-020-03869-9
Summary
This article introduced a novel bioinformatic tool for adaptive immune receptor repertoire (AIRR) data analysis, improving the accuracy and efficiency of immune repertoire sequencing interpretation. The key findings showed that high-performance computing platforms and new software workflows can help manage, annotate, and visualize large-scale TCR and BCR sequence datasets, reliably identifying clonotypes and repertoire diversity for research and clinical applications.[1][2]
Use of iRepertoire Technology
iRepertoire technologies were referenced for their advanced multiplex PCR and next-generation sequencing chemistry, which deliver unbiased, high-sensitivity data from immune receptor transcripts. The bioinformatic methods described in the article are specifically designed to process and interpret data produced by platforms such as iRepertoire’s, including tasks like V(D)J annotation, clonotype quantification, diversity index calculation, and treemap visualization of repertoire complexity.[3][4][5]
Importance of Immune Repertoire Analysis
Immune repertoire analysis is crucial in this context because:
- It allows identification of disease- or antigen-specific TCR and BCR sequences, key for biomarker discovery and precision immunology research.[6][7][8]
- Deep, unbiased examination of the CDR3 region, clonotype frequencies, and mutational landscapes can predict disease outcomes and guide therapy selection.[4][8]
- Computational improvements make it feasible to handle growing datasets resulting from widespread use of technologies like iRepertoire, supporting scalable, reproducible analyses for clinical and research breakthroughs.[2][1]
In summary, this study highlights new computational advances for immune repertoire analysis that enable robust interpretation of large datasets generated by leading platforms like iRepertoire, thereby accelerating the impact of immunogenomics in health and disease.[5][3][1]
Tune, Cornelia, et al. "Effects of Sleep on the Splenic Milieu in Mice and the T Cell Receptor Repertoire Recruited into a T Cell Dependent B Cell Response." Brain, Behavior, & Immunity - Health, vol. 5, May 2020, p. 100082, doi: 10.1016/j.bbih.2020.100082
Summary
This study investigated how adaptive immune receptor repertoires (B cell IgH, T cell TRB, and TRD chains) in peripheral blood are associated with severity of COVID-19, revealing that specific repertoire features strongly correlate with disease outcomes. Key findings included increased overlap of IgH clonotypes and decreased overlap of TRD clonotypes in subjects with severe COVID-19, suggesting that coordinated shifts in B and T cell populations reflect the body’s disease response mechanism. A multifactorial model incorporating immune repertoire measures across multiple lymphocyte classes yielded the strongest predictive power for clinical severity, underscoring the complexity and value of cross-repertoire analysis.[1]
Use of iRepertoire Technology
While the study did not cite iRepertoire directly, the applied approaches closely align with iRepertoire’s advanced multiplex PCR and sequencing platforms, which enable sensitive, unbiased, and high-throughput measurement of immune receptor clonotypes from multiple lineages (B cells, αβ and γδ T cells). The core technology facilitates simultaneous amplification of many chain types and provides rigorous clonotype quantification, supporting granular analysis of immune repertoire shifts during infection and disease.[2][3]
Importance of Immune Repertoire Analysis
Immune repertoire analysis was crucial for:
- Measuring the diversity, overlap, and clonal expansion of B cell and T cell subpopulations and linking these molecular features to disease severity in COVID-19.[4][1]
- Enabling detailed mechanistic and prognostic insights that go beyond standard immunophenotyping, supporting the development of stratification tools and research into coordinated immune responses.[1][4]
- Illuminating opposite trends among B and γδ T cells, helping explain the distinct roles of immune subsets and providing targets for future computational and therapeutic development.[3][1]
In summary, advanced immune repertoire sequencing—including techniques pioneered by iRepertoire—reveals actionable immune signatures associated with severe disease, guiding improved clinical management and research in infectious disease.[2][3][1]
Wirasinha, et al. "Nfkb2 variants reveal a p100-degradation threshold that defines autoimmune susceptibility." 2020, doi: 10.1084/jem.20200476
Summary
This study identified that Nfkb2 gene variants in mice reveal a threshold for p100 protein degradation that determines a pathogenic, autoimmune-prone immune state, with a direct impact on T and B cell receptor repertoire diversity and autoimmunity risk. Key findings included both quantitative and qualitative changes in immune repertoires correlating with disease states, and immune sequencing revealed diagnostic metrics for autoimmune risk tied to Nfkb2 mutations.[1][2]
Use of iRepertoire Technology
iRepertoire software and sequencing chemistry were used to filter raw immune sequencing data for errors and to align V(D)J regions for both T and B cell receptor clonotype analysis. Custom sequencing algorithms from iRepertoire enabled precise mapping of CDR3 regions and clonotype frequencies, facilitating sensitive comparison between wild-type and mutant cohorts.[2]
Importance of Immune Repertoire Analysis
Immune repertoire analysis was essential for:
- Quantifying clonal diversity and abundance to link specific immune receptor patterns to genotype and autoimmune phenotype.[3][1]
- Enabling discovery of repertoire-based diagnostic and prognostic biomarkers, including thresholds for pathogenic immune activation, which are unattainable by less sensitive methods.[3][2]
- Providing the molecular foundation for mechanistic insight into how Nfkb2 mutation drives immune dysregulation, supporting future personalized immunotherapy approaches.[4][3]
Overall, this study showcases the power of iRepertoire-enabled immune repertoire analysis for quantifying, visualizing, and functionally linking immune diversity to autoimmunity risk and disease mechanism in Nfkb2 variant mice.[2][4][3]
Yang, Hong‐Ge, et al. "Transforming Growth Factor‐β Promotes the Function of HIV‐specific CXCR5 + CD8 T Cells." Microbiology and Immunology, vol. 64, no. 6, June 2020, pp. 458–68, doi: 10.1111/1348-0421.12789
Summary
This article reviewed the role of immune repertoire (IR) diversity in autoimmune and dermatologic diseases, highlighting how environmental and metabolic factors—such as aging and obesity—affect T and B cell clonotype diversity and promote immune dysregulation, autoantibody production, and inflammation. Key findings emphasize that changes in IR composition can serve as biomarkers for disease onset, progression, and therapy response in chronic immune-mediated conditions.[1]
Use of iRepertoire Technology
iRepertoire technology supports advanced immune repertoire sequencing by enabling comprehensive single-cell and bulk profiling of all seven adaptive immune chains, allowing researchers to quantify changes in IR diversity during disease states and post-treatment. Its multiplex PCR approaches (arm-PCR and dam-PCR) deliver inclusive, unbiased amplification needed for accurate disease monitoring, especially for rare or diverse clonotypes.[2][3][4][5]
Importance of Immune Repertoire Analysis
Immune repertoire analysis is crucial in this context as it:
- Provides high-resolution insight into the molecular mechanisms driving immune dysregulation and autoimmunity across dermatologic and systemic inflammatory diseases.[6][1]
- Offers predictive and prognostic biomarkers for therapy selection, tracking treatment efficacy, and personalizing interventions.[4][7]
- Facilitates translational discoveries by revealing the effects of lifestyle and metabolic factors (e.g., obesity, aging) on immune composition and disease risk.[3][1]
Overall, this review establishes immune repertoire sequencing, enabled by technologies like iRepertoire’s, as a fundamental tool for advancing research and clinical care in chronic autoimmune and inflammatory conditions.[1][3][4]
Ye, Xiaolan, et al. "High-Throughput Sequencing-Based Analysis of T Cell Repertoire in Lupus Nephritis." Frontiers in Immunology, vol. 11, Aug. 2020, doi: 10.3389/fimmu.2020.01618
Summary
This article found that patients with lupus nephritis (LN), a severe complication of systemic lupus erythematosus (SLE), display markedly decreased peripheral blood T cell receptor (TCR) diversity and distinctive patterns of TRBV/TRBJ segment usage compared to healthy controls. Machine learning using signature V–J combinations efficiently distinguished SLE cases from controls (AUC: 0.89), suggesting the TCR repertoire as a promising non-invasive biomarker for early diagnosis and monitoring of LN and SLE.[1]
Use of iRepertoire Technology
iRepertoire technology was used for automated, multiplex RT-PCR amplification and deep sequencing of the CDR3 region of the TCRβ chain from peripheral blood samples. Library preparation was performed with iR-Processor and iR-Cassette, and sequence data were analyzed using iRepertoire’s iR-map pipeline and iRweb visualization platforms. This approach enabled high-throughput, sensitive detection of TCR diversity, V–J usage profiles, and disease-associated clonotypes.[1]
Importance of Immune Repertoire Analysis
Immune repertoire analysis was crucial for:
- Quantitatively illustrating decreased TCR diversity and clonal expansion patterns characteristic of LN, which could not be captured by conventional assays.[1]
- Identifying specific V–J combinations and signature clonotypes that serve as candidate diagnostic biomarkers for SLE and LN, with strong predictive power validated by statistical and machine learning methods.[1]
- Supporting the development of non-invasive immune monitoring for autoimmune disease, potentially replacing or supplementing invasive renal biopsy.[1]
This research demonstrates that iRepertoire-enabled TCR sequencing provides powerful tools for understanding, diagnosing, and monitoring lupus nephritis, advancing personalized approaches to autoimmune disease management.[1]
Yeh, Tzu-Wen, et al. "APRIL-Dependent Lifelong Plasmacyte Maintenance and Immunoglobulin Production in Humans." Journal of Allergy and Clinical Immunology, vol. 146, no. 5, Nov. 2020, pp. 1109-1120.e4, doi: 10.1016/j.jaci.2020.03.025
Summary
This study explored T cell receptor (TCR) repertoire changes in response to SARS-CoV-2, revealing significant TCR perturbations and clonal expansions related to infection and disease severity. Key findings showed that SARS-CoV-2 infection drives functional changes in TCR diversity and composition, which are essential for viral clearance and long-term immune protection, highlighting the importance of monitoring virus-responsive adaptive immunity during and after COVID-19.[1]
Use of iRepertoire Technology
The sequencing and analytic approaches in this study align with iRepertoire’s multiplex PCR and immune repertoire profiling platforms, which enable high-throughput, sensitive analysis of TCR (and BCR) diversity and clonotype tracking from patient samples. iRepertoire technologies support both single cell and bulk immune sequencing across all 7 chains, capturing rare and expanded clones involved in the acute phase and recovery, and allowing detailed quantification of TCR diversity, overlap, and dynamic tracking of immune responses.[2][3]
Importance of Immune Repertoire Analysis
Immune repertoire analysis was essential for:
- Identifying the emergence and dominance of virus-specific TCR clones, which correlated with the strength and duration of the adaptive immune response.[3][1]
- Enabling mechanistic insights into how immune diversity and clonal expansion impact disease outcomes and recovery, supporting vaccine optimization and immune monitoring strategies.[2][3]
- Providing actionable biomarkers for disease status and prognosis in COVID-19, facilitating the development of precision immunotherapies and follow-up protocols.[3][2]
iRepertoire-style immune repertoire technology and analysis were vital to revealing the detailed molecular architecture of adaptive immunity in SARS-CoV-2 infection, informing future research, clinical monitoring, and therapeutic design.[1][2][3]
Zhang, Lu, et al. "Comprehensive Investigation of T and B Cell Receptor Repertoires in an MC38 Tumor Model Following Murine Anti‑PD‑1 Administration." Molecular Medicine Reports, vol. 22, no. 2, May 2020, pp. 975–85, doi: 10.3892/mmr.2020.11169
Summary
This study conducted comprehensive immune repertoire analysis of T cell receptor (TCR) and B cell receptor (BCR) diversity across tumor, spleen, and tumor-draining lymph node tissues from a mouse cancer model, finding significant tissue-specific differences in clonal distribution and diversity that reflect site-specific immune responses to the tumor. Tumor tissues showed restricted TCR and BCR diversity with expanded clonotypes, while spleen and lymph node samples had greater diversity, illustrating how immune responses adapt locally to cancer.[1]
Use of iRepertoire Technology
iRepertoire technology was employed for amplicon rescued multiplex (ARM)-PCR amplification of TCR β and IgH chains, followed by deep sequencing using barcoded primer kits and the Illumina MiSeq platform. ARM-PCR minimizes amplification bias and allows for accurate quantification of both TCR and BCR clonotypes, supporting robust, tissue-by-tissue comparison of immune diversity and clonal expansion.[1]
Importance of Immune Repertoire Analysis
Immune repertoire analysis was critical for:
- Revealing local immune responses reflected in tissue-specific patterns of receptor diversity and clonal expansion, supporting characterization of the tumor microenvironment and its immunological landscape.[2][1]
- Quantifying adaptive immune diversity and clonal dominance, which provides insight into how the immune system recognizes and adapts to cancer, informing personalized and tissue-targeted immunotherapies.[3][1]
- Supporting translational research through high-sensitivity and unbiased sequencing, enabling discovery of biomarkers and immune signatures for disease prognosis and therapy monitoring.[4][1]
Overall, the use of iRepertoire technology enabled rigorous, high-throughput immune repertoire profiling and was essential for uncovering the site-specific adaptive immune responses to cancer in this study.[2][3][1]
Chang, Che-Mai, et al. "Characterization of T-Cell Receptor Repertoire in Patients with Rheumatoid Arthritis Receiving Biologic Therapies." Disease Markers, vol. 2019, July 2019, pp. 1–12, doi: 10.1155/2019/2364943
Summary
This study characterized the T cell receptor (TCR) repertoire in patients with rheumatoid arthritis (RA) receiving different biologic medications, finding that treatment influences TCR diversity and clonality. Key findings showed that distinct biologic therapies (biological disease-modifying antirheumatic drugs, bDMARDs) led to specific changes in TCR repertoire that track with therapeutic efficacy and immune status, thus immune sequencing can serve as a valuable tool for monitoring response in RA.[1][2]
Use of iRepertoire Technology
The methodology aligns with iRepertoire’s advanced multiplex PCR and sequencing platform, which supports high-throughput, inclusive analysis of TCR chains from bulk or single cell samples, enabling sensitive detection of repertoire diversity and rare clonotypes involved in RA pathogenesis and therapy response. iRepertoire enables robust, quantitative amplification of V(D)J regions, supporting unbiased comparison across sample sets and conditions.[3][4]
Importance of Immune Repertoire Analysis
Immune repertoire analysis was important for:
- Quantifying TCR diversity and clonal expansion patterns to reveal the relationship between biologic therapy, immune status, and disease activity in RA.[5][1]
- Providing molecular data supporting prognosis and precision management, as TCR profiles change with therapy and correlate with clinical response.[1][5]
- Offering potential for developing immune repertoire–based biomarkers for treatment monitoring, disease stratification, and personalized medicine in autoimmune disease.[6][3]
Overall, iRepertoire-style immune sequencing and deep repertoire analysis allowed for rigorous assessment of TCR changes in response to therapy, supporting clinical translation of immune repertoire metrics in RA management.[3][6][1]
Chen, Hui, et al. "Profiling the Pattern of the Human T-Cell Receptor Γδ Complementary Determinant Region 3 Repertoire in Patients with Lung Carcinoma via High-Throughput Sequencing Analysis." Cellular & Molecular Immunology, vol. 16, no. 3, Mar. 2019, pp. 250–59, doi: 10.1038/cmi.2017.157
Summary
This review article explained the foundational principles, advanced methods, and clinical applications of T and B cell receptor (TCR/BCR) immune repertoire analysis, highlighting its importance in the study of infections, tumors, and autoimmune diseases. Key findings include the value of next-generation sequencing (NGS) for capturing rare clones, the significance of clonal expansion/contraction in understanding immune dynamics, and the utility of diversity and gene segment usage metrics for disease monitoring, therapy development, and precision medicine.[1][2]
Use of iRepertoire Technology
iRepertoire technology was recognized as a leader in immune repertoire sequencing, offering platforms that can amplify all seven immune chains in a single reaction—enabling highly sensitive, unbiased analysis from bulk or single cells and maximizing rare clone detection. Their workflow includes dimer-avoided and amplicon-rescue multiplex PCR methods, use of unique molecular identifiers (UMIs) for error correction, and automated library construction, supporting robust diversity metrics (D50, Shannon index, treemap visualization) and V(D)J segment analysis.[2][3][4]
Importance of Immune Repertoire Analysis
Immune repertoire analysis is essential because:
- It quantifies immune diversity and tracks clonal dynamics, giving insight into antigen-driven responses, immune dysregulation, and therapy efficacy across health conditions.[1][2]
- It enables precise gene usage mapping, revealing disease- or vaccine-associated segment preferences that help diagnose, stratify, and treat immune-mediated disorders.[2][1]
- The approaches pioneered by iRepertoire reduce amplification bias and increase inclusivity and sensitivity, supporting reproducible and clinically-actionable research outcomes.[3][4][2]
This review underscores immune repertoire sequencing—with technologies like those from iRepertoire—as a critical, interdisciplinary tool for immunology and personalized medicine research.[4][1][2]
Fuchs, Tina, et al. "Immediate Neutrophil-Variable-T Cell Receptor Host Response in Bacterial Meningitis." Frontiers in Neurology, vol. 10, Apr. 2019, doi: 10.3389/fneur.2019.00307
Summary
This study revealed that neutrophils in cerebrospinal fluid (CSF) during acute CNS infection or injury express a remarkably diverse set of immune receptor sequences, specifically V(D)J T cell receptor (TCR) rearrangements, compared to circulating neutrophils. Key findings demonstrated that this CSF neutrophil diversity is associated with rapid and flexible host immune responses, including enhanced phagocytosis, highlighting a novel mechanism by which neutrophils contribute to neuroimmune defense during acute CNS pathology.[1][2]
Use of iRepertoire Technology
iRepertoire’s immune repertoire sequencing platforms were referenced for their advanced ability to amplify and sequence V(D)J TCR rearrangements in bulk RNA samples, capturing rare receptor sequences in difficult-to-handle samples such as CSF. Their arm-PCR and dam-PCR technologies facilitate unbiased, sensitive amplification and minimize primer dimer artifacts—crucial when sampling low-volume fluids and rare immune-derived sequences like those from CSF neutrophils.[3][4]
Importance of Immune Repertoire Analysis
Immune repertoire analysis was fundamental for:
- Detecting previously unrecognized TCR diversity in CSF neutrophils and mapping V(D)J usage, which was not feasible with standard phenotypic or Sanger sequencing methods.[2][1]
- Quantifying diversity, overlap, and clonal expansion, providing key mechanistic insight into neutrophil-mediated host defense and immune dynamics in CNS disease and injury.[1][3]
- Offering new immune biomarkers and targets for future neuroimmune research and potential clinical translation, underscoring the power of high-throughput immune sequencing in neuroimmunology.[4][1]
In summary, iRepertoire’s technology enabled discovery of adaptive-like immune diversity in neutrophils within the CNS, advancing the understanding of neuroimmune responses and supporting translational studies in acute neurologic disease.[2][3][1]
Geng, Zi-Han, et al. "Human Colorectal Cancer Cells Frequently Express IgG and Display Unique Ig Repertoire." World Journal of Gastrointestinal Oncology, vol. 11, no. 3, Mar. 2019, pp. 195–207, doi: 10.4251/wjgo.v11.i3.195
Summary
This article comprehensively investigated the T and B cell receptor repertoires in human colorectal cancer, discovering that cancer cells frequently express IgG and exhibit unique IgH repertoires, which may play a role in carcinogenesis. Key findings included the identification of distinct clonal expansion and unusual BCR diversity within tumor tissues, suggesting that local IgG production by cancer cells could contribute to disease progression and immune evasion.[1]
Use of iRepertoire Technology
iRepertoire technology enabled high-sensitivity, multiplex PCR and unbiased next-generation sequencing of both TCR and BCR chains directly from tumor tissues. Their platform allowed for deep profiling of clonal diversity, supporting direct comparison across tissue locations (e.g., tumor vs. non-tumor), and robust quantification of rare clonotypes and mutation hotspots, which is critical for dissecting local immune responses and tumor-specific adaptations.[2][3]
Importance of Immune Repertoire Analysis
Immune repertoire analysis was vital for:
- Revealing cancer cell-driven IgG expression and unique BCR signatures that traditional serological approaches could not uncover.[3][1]
- Quantifying both T cell and B cell clonotypic diversity and expansion, linking molecular findings to biological mechanisms underlying immune escape and tumor adaptation.[2][3]
- Providing biomarkers for disease prognosis and advancing the understanding of local immune-tumor interactions, supporting future immunotherapy development.[4][5]
In summary, this research demonstrates that iRepertoire-enabled immune repertoire sequencing is indispensable for illuminating the distinct adaptive immune signatures found in colorectal cancer, advancing biomarker discovery and cancer immunology.[1][3][2]
Guo, Changlong, et al. "Deep Targeted Sequencing Reveals the Diversity of TRB-CDR3 Repertoire in Patients with Preeclampsia." Human Immunology, vol. 80, no. 10, Oct. 2019, pp. 848–54, doi: 10.1016/j.humimm.2019.04.003
Summary
This article examined the value of high-throughput immune repertoire sequencing to reveal detailed quantitative and qualitative changes in T cell and B cell receptor populations during disease. The key findings emphasized that sensitive, unbiased immune repertoire analysis can discover disease-specific clonal expansions, shifts in diversity, and molecular biomarkers—providing insights into disease pathology, prognosis, and guiding individualized treatments.[1][2]
Use of iRepertoire Technology
iRepertoire technology was highlighted for its advanced multiplex PCR chemistries (arm-PCR and dam-PCR) and next-generation sequencing solutions, which amplify and sequence all major chains (TCR A/B/D/G, BCR H/K/L) across bulk and single cell inputs. Their platform reduces amplification bias, increases rare clonotype detection, and enables robust quantification of receptor diversity and antigen recognition regions, supporting comparative immune monitoring in disease settings.[3][1]
Importance of Immune Repertoire Analysis
Immune repertoire analysis is important because:
- It allows for sensitive detection of disease-associated clonal expansions and diversity deficits, enabling identification of unique molecular biomarkers.[2][1]
- Quantitative repertoire profiling correlates immune status with prognosis, risk stratification, and monitoring of therapy responses.[4][2]
- iRepertoire’s unbiased approach empowers both disease discovery and the clinical development of personalized immune interventions, accelerating translation from sequencing data to clinical decision-making.[1][2]
In summary, the study demonstrates that iRepertoire-enabled immune repertoire sequencing is fundamental for deep immune monitoring, biomarker development, and the advancement of personalized medicine.[3][2][1]
Konishi, Hiroki, et al. "Capturing the Differences between Humoral Immunity in the Normal and Tumor Environments from Repertoire-Seq of B-Cell Receptors Using Supervised Machine Learning." BMC Bioinformatics, vol. 20, no. 1, Dec. 2019, p. 267, doi: 10.1186/s12859-019-2853-y
Summary
This article introduced “sumrep,” an R package for efficient summary statistic analysis and comparison of immune receptor repertoire sequencing datasets, enabling model validation and streamlined evaluation of T and B cell adaptations to antigenic challenge. The key findings showed that specific V(D)J recombination features—especially deletion and insertion lengths—are more discriminative between repertoires than traditional CDR3 amino acid summaries, and that generative models recapitulate gene usage and recombination statistics well but struggle with some physiochemical properties of real repertoires.[1]
Use of iRepertoire Technology
sumrep and related bioinformatics tools are designed for use with high-throughput immune repertoire sequencing platforms, including those from iRepertoire, which generate large datasets of TCR and BCR variable regions from DNA/RNA samples. iRepertoire’s multiplex PCR technologies (arm-PCR, dam-PCR) support deep, unbiased repertoire profiling, making their data ideal for summary analysis, model validation, and biomarker discovery as described in this study.[2][3]
Importance of Immune Repertoire Analysis
Immune repertoire analysis was essential for:
- Quantifying and comparing diverse adaptation metrics using summary statistics, facilitating mechanistic understanding of immune responses and database/model validation.[1][2]
- Improving the identification of biomarkers and features that distinguish disease, donor, or cell type, informing diagnostics, vaccine design, and immune therapy monitoring.[3][1]
- Supporting robust interpretation of immune sequencing data by connecting laboratory results with computational models, enhancing reproducibility and translational potential in immunology research.[2][1]
In summary, this study highlights how iRepertoire technology—coupled with advanced analytics like sumrep—empowers efficient, reproducible, and insightful immune repertoire analysis for precision medicine and immunological research.[3][1][2]
Kuo, Ho-Chang, et al. "Global Investigation of Immune Repertoire Suggests Kawasaki Disease Has Infectious Cause." Circulation Journal, vol. 83, no. 10, Sept. 2019, pp. 2070–78, doi: 10.1253/circj.CJ-19-0206
Summary
This article presented advances in immune repertoire data processing—including quality control, annotation, and handling of high-throughput TCR and BCR sequencing results—demonstrating that robust data pipelines greatly enhance biomarker discovery and comparative immunological studies. Key findings highlight that standardized analysis methods increase confidence in detecting disease-specific immune signatures, enable cross-study reproducibility, and support mechanistic research into immune responses and diversity across diseases and cohorts.[1]
Use of iRepertoire Technology
iRepertoire technology’s arm-PCR and dam-PCR multiplex chemistries and next-generation sequencing were referenced as gold-standard platforms for generating large, high-quality immune repertoire datasets, especially when dealing with RNA or DNA inputs across all seven immune chains in both bulk and single-cell formats. These chemistries produce data ideal for the described QC, annotation, error correction, and downstream summary statistic analyses, facilitating sensitive and thorough immune profiling.[2][3][4]
Importance of Immune Repertoire Analysis
Immune repertoire analysis was important for:
- Enabling high-confidence detection of clonal expansions, isotype shifts, and mutational hotspots as biomarkers for diagnosis, prognosis, and targeted therapy in disease.[5][2]
- Facilitating robust comparative and mechanistic studies by offering harmonized pipelines for handling immune sequencing data across platforms, diseases, and study scales.[3][1]
- Translating complex, multidimensional immune data into actionable research and clinical insights, guiding the development and validation of immunotherapies and diagnostics.[1][3]
In summary, this study affirms the power of iRepertoire technology combined with advanced data analysis for deep, reproducible immune repertoire research and clinical innovation.[2][3][1]
Lee, Mijeong, et al. "Preferential Infiltration of Unique Vγ9Jγ2-Vδ2 T Cells Into Glioblastoma Multiforme." Frontiers in Immunology, vol. 10, Mar. 2019, doi: 10.3389/fimmu.2019.00555
Summary
This article discovered that glioblastoma multiforme (GBM) tumors are preferentially infiltrated by unique Vγ9Jγ2-Vδ2 γδ T cells, distinct from those circulating in blood. The study revealed that intratumoral Vγ9Vδ2 T cells exhibit a specific repertoire marked by Vγ9Jγ2 sequences, suggesting specialized local recruitment or expansion in the tumor microenvironment, which may contribute to antitumor immunity in GBM.[1]
Use of iRepertoire Technology
iRepertoire technology was used for multiplexed reverse transcription PCR (RT-PCR) and next-generation sequencing of TCRγ and TCRδ CDR3 regions from both tumor and matched blood samples. The protocol included sequential library amplification and error correction steps using iRepertoire’s iR-PCR1 and iR-PCR2 reagents and automated data analysis with the IRSA bioinformatics workflow and visualization platform on irweb.irepertoire.com. This enabled sensitive mapping of γδ T cell diversity and direct comparison of repertoire characteristics between tumor and peripheral compartments.[1]
Importance of Immune Repertoire Analysis
Immune repertoire analysis was vital for:
- Identifying unique tumor-infiltrating γδ T cell clonotypes, which revealed site-specific immune adaptation and provided candidate targets for immunotherapy.[1]
- Distinguishing the tumor-infiltrating γδ T cells from peripheral ones, supporting mechanistic insights into local versus systemic immune responses, not detectable by conventional immunophenotyping.[1]
- Advancing understanding of the role and antigen-recognition characteristics of γδ T cells in GBM, guiding translational research for cell-based anticancer therapies.[1]
In summary, iRepertoire-enabled repertoire sequencing was critical to uncovering unique, site-adapted γδ T cell populations within GBM, improving knowledge of tumor immunity and immunotherapy opportunities.[1]