Creative Biolabs is able to provide the unique T-cell receptor (TCR) repertoire analysis service for our customers all over the world. With our powerful Magic™ platform, scientists from Creative Biolabs are confident in sequencing CDR regions of the whole four types of TCR chains (α, β, γ, and δ) accurately and comprehensively.

Background

The effective TCR repertoire plays an essential role in the adaptive immune system. TCR, which locates on the T-cell surface, is responsible for interacting with peptide fragments of antigens that bound to major histocompatibility complex (MHC) molecules. In general, most of TCR consists of an α chain and a β chain as a heterodimer, and a minority of TCR is formed by a γ chain and a δ chain as an alternative. Commonly, for a healthy human, α/β TCR accounting for 95% and other 5% is γ/δ TCR. While the proportion between α/β TCR and γ/δ TCR is changeable due to ontogenesis, disease influence or different species. Similar to half of the Fab fragment of an antibody, each TCR chain is composed of a constant and a variable region which also has three complementarity determining regions (CDRs). Meanwhile, the TCR α chain and γ chain are generated by VJ recombination (just like the light chain of an antibody), and the β chain and δ chain undergo VDJ recombination (similar to the heavy chain of an antibody). During this rearrangement mechanism, the nucleotide additions or deletions at the junctions have endowed the TCR repertoire with essential diversity. In this way, the sequencing and analysis of TCR repertoire is a meaningful direction to enhance the understanding of the immune system, especially under different stimulation, such as infections, autoimmune diseases, and cancers, and contribute to discovering new therapeutic agents.

Magic™ TCR Repertoire Sequencing Service

To achieve the best high-throughput sequencing capacity, Creative Biolabs has integrated the popular next generation sequencing (NGS) technology and other specific techniques into our unique Magic™ platform. This platform can be widely used in large-scale sequencing but also available to be specially designed for certain service. For the sequencing of TCR repertoire, the Magic™ IR-seq platform permits RNA from human or mice as a template to amplify and sequence the complementary determining region (CDR) of whether α, β, γ or δ chain of TCR. Through this excellent platform, our clients can obtain the sequence data of whole covered CDR 3 regions of the interested TCR chain from either human or mice, which has involved most of the hypermutation information.

Besides regular sequencing analysis of the TCR repertoire, we also provide a series of custom analysis options including but not limit to:

• Magic™ TCR Repertoire Profiling for T Cell Infiltration Analysis
• Magic™ TCR Repertoire Analysis for Invariant T Cell Identification
• Magic™ TCR Repertoire Analysis for Antigen-specific T Cells Identification
• Magic™ TCR Repertoire Analysis for Minimal Residual Disease Quantification
• Magic™ TCR Repertoire Analysis for Regulatory T Cells Identification
• Magic™ Ultra-Sensitive Detection of Rare T Cell Clones
• Magic™ TCR γ δ Repertoire Profiling
• Magic™ Tumor-associated TCR Repertoires Profiling by RNA Sequencing

Features of Magic™ platform for repertoire analysis

• Comprehensive TCR repertoire from RNA of either human or mice
• Specific capture primers
• High fidelity amplification method
• Advanced high-throughput sequencing platform

Creative Biolabs is a long-term expert in the field of immunology who has extensive experience and advanced technology platform for NGS sequencing. Our scientists have accomplished over hundreds of sequencing projects and accumulated sufficient knowledge and understanding of the adaptive immune system. We are pleased to offer the best service with the most accurate sequencing results for our global customers.

TCR repertoire analysis

• Identification of Specific V and J Genes and the Assessment of Clonality and Diversity of T Cells by TCR Repertoire Analysis

Fig. 1 T-cell receptor repertoire construction and analysis.¹

The study explores the immune heterogeneity between systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) using multi-omics data, particularly T-cell receptor (TCR) and B-cell receptor (BCR) repertoire analyses. TCR repertoire analysis, a key aspect of this research, allows for the identification of specific TCR V and J genes, providing insights into the clonality and diversity of T cells in SLE and RA. The study's results indicate that while there is no significant difference in the top 10 clonotypes between the groups, the diversity of TCR CDR3 sequences was higher in RA compared to healthy controls. This finding suggests that TCR diversity could be a key factor in the pathogenesis of RA, potentially serving as a biomarker for disease progression or response to therapy. The application of TCR repertoire analysis in this study highlights its importance in understanding autoimmune disease mechanisms, which could lead to the development of targeted therapies and personalized treatment strategies.

FAQ

1. What is TCR repertoire analysis and why is it important in immunology research?

   TCR repertoire analysis involves sequencing and analyzing the diversity of T-cell receptors (TCRs) within an organism's immune system. This analysis is crucial for understanding how the immune system recognizes and responds to a wide range of antigens, including those from pathogens, tumors, and autoimmune triggers. It helps researchers identify specific TCR sequences associated with diseases, enabling the development of targeted therapies and personalized medicine approaches.

2. How is TCR repertoire analysis performed?

   TCR repertoire analysis is performed using high-throughput sequencing technologies, such as next-generation sequencing (NGS). The process begins with the isolation of T cells, followed by the extraction of RNA or DNA. The TCR regions, particularly the V, D, and J segments, are then amplified and sequenced. Bioinformatics tools are used to analyze the data, providing insights into the diversity, clonality, and specific TCR sequences present in the sample.

3. What are the applications of TCR repertoire analysis in clinical research?

   TCR repertoire analysis has multiple applications in monitoring immune responses to infections, vaccines, and cancer immunotherapies. It is also used to study autoimmune diseases by identifying abnormal TCR sequences that may contribute to disease pathogenesis. Additionally, TCR repertoire data can be used to track the effectiveness of treatments and to develop new therapeutic strategies that target specific TCRs involved in disease processes.

4. How does TCR repertoire analysis contribute to cancer immunotherapy?

   TCR repertoire analysis helps in understanding how T cells recognize and attack tumor cells. By analyzing the TCR diversity in cancer patients, researchers can identify specific TCR sequences associated with effective anti-tumor responses. This information can be used to design personalized immunotherapies, such as TCR-engineered T cells, which target the unique TCRs found in a patient's tumor.

5. What challenges are associated with TCR repertoire analysis?

   One of the main challenges in TCR repertoire analysis is the immense diversity and complexity of TCRs, which requires sophisticated bioinformatics tools to accurately analyze and interpret the data. Additionally, obtaining high-quality samples and ensuring consistent sequencing depth can be difficult. Another challenge is the need for robust computational methods to handle the large datasets generated, requiring expertise in both immunology and computational biology.

6. Can TCR repertoire analysis be used to diagnose autoimmune diseases?

   TCR repertoire analysis can be used to diagnose and understand autoimmune diseases. By analyzing the TCR diversity and identifying specific TCR sequences associated with autoantigens, researchers can gain insights into the mechanisms driving autoimmune responses. This information can help in the early diagnosis of autoimmune diseases and in developing targeted treatments that modulate the immune system to reduce or prevent harmful autoimmune attacks.

7. How does TCR repertoire analysis differ from BCR Repertoire Analysis?

   TCR repertoire analysis focuses on the diversity of T-cell receptors, which are involved in recognizing antigens presented by other cells, leading to a broader immune response. In contrast, BCR Repertoire Analysis studies B-cell receptors, which directly recognize antigens and lead to the production of antibodies. Both analyses are essential for understanding the adaptive immune response, but they target different components of the immune system and have distinct applications in research and clinical settings.

8. What role does TCR repertoire analysis play in understanding infectious diseases?

   TCR repertoire analysis plays a critical role in understanding how the immune system responds to infectious diseases by identifying the specific TCRs that recognize and respond to pathogen-derived antigens. This analysis helps researchers track the evolution of the immune response during infection, identify protective TCR sequences, and develop vaccines or therapies that enhance the immune system's ability to fight off infections.

9. How does TCR repertoire analysis help in the development of personalized medicine?

   TCR repertoire analysis is a cornerstone of personalized medicine because it provides detailed information about an individual's immune response. By analyzing the unique TCR repertoire of a patient, clinicians can design tailored treatments that target specific TCR sequences associated with disease. This approach is particularly valuable in cancer treatment, where personalized immunotherapies can be developed based on the patient's TCR profile, leading to more effective and targeted therapies.

Resources

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