With years of research and development experience in the field of immunology, Creative Biolabs has owned a group of scientists who have the distinguished understanding of the adaptive immune system. We are proficient in providing high-quality service of TCR γ δ CDR3 repertoires profiling by our Magic™ TCR repertoire analysis platform. Our data will provide a comprehensive understanding of the diversity of TCR γ δ repertoire in the physiological condition, which is an important clue to the underlying mechanism of γ δ T cell recognition of tumor antigens.
T lymphocytes are classified structurally into two subtypes according to the different heterodimers TCR α β and γ δ. γ δ T cells function as sentinels in early host response to infections and malignancies. Although γ δ T cells account for a minor fraction in the peripheral blood of healthy individuals, they constitute a major subset of T cells in the intestine and skin. They serve as a bridge between innate and adaptive immunity in the first line defense of tumorigenesis and pathogen infection. Similar to TCR α β, TCR γ δ is also generated by the rearrangement of germline gene V-(D)-J-C fragments. The antigen binding site of TCR γ δ consists of six complementary determinant regions (CDRs). γ δ T cells show more connection diversity compared with TCR α β. The diversity of TCR γ δ CDR3 repertoire is quite dispersed and individually different. The TCR δ chain (TRD) repertoire displayed more diversity and showed less sharing sequences among individuals compared with TCR γ chain (TRG). Previously, the analysis of TCR γ δ CDR3 repertoire is restricted by limited techniques based on clonal sequencing. Therefore, the detailed characteristics of the TCR γ δ CDR3 repertoire remain unclear. A comprehensive analysis would answer fundamental questions about the diversity of the TCR γ δ CDR3 repertoire and elucidate the mechanism underlying γ δ T cell recognition of pathogens and tumor antigens.
Creative Biolabs has established a high-throughput Magic™ TCR repertoire analysis platform for TCR sequencing. Our scientists can perform a comprehensive analysis of TCR γ δ by immune repertoire sequencing. After the extraction of total RNA from peripheral blood mononuclear cells (PBMC) or tissues, RT-PCR and arm-PCRs were performed to amplify the cDNAs. cDNAs are normalized by the γ δ T cell percentage in each sample and then sequenced on our powerful Magic™ platform. The diversity, N-addition length distribution and germline gene V and J segment usage of CDR3 γ and CDR3 δ repertoire are analyzed through our unique bioinformatics peptides.
Equipped with world-leading technology platforms and professional scientific staff in the field of immunology, scientists of Creative Biolabs have performed over hundreds of TCR repertoire sequencing projects and accumulated sufficient experiences. Our scientists can perform a comprehensive analysis of TCR γ δ repertoire for all our global customers.
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Other optional Magic™ TCR repertoire analysis services:
Fig.1 Naked mole-rat NK-like effector γδ T are enriched for invariant TCR sequences.1
This study focuses on the naked mole-rat's γδ T cell-based immunity, particularly the invariant Vγ4-2/Vδ1-4 TCR repertoire, exploring its potential contribution to cancer resistance. The significance of this research lies in understanding the immune system's role in the naked mole-rat's exceptional cancer resistance, as this species lacks conventional NK cells. Results indicate the presence of invariant γδ T cells expressing NK-like cytotoxic genes, which may participate in tumor immunosurveillance. TCR γ/δ repertoire profiling revealed a highly oligoclonal structure dominated by public invariant TCR sequences, produced until adulthood. This profiling is important because it highlights how invariant γδ T cells may offer a continuous supply of effector cells that contribute to the naked mole-rat's resistance to cancer, potentially offering insights for developing novel immunotherapeutic approaches.
TCR γ/δ CDR3 repertoires profiling involves sequencing and analyzing the complementarity-determining region 3 (CDR3) of T-cell receptors (TCRs) on γ/δ T cells. This region is highly variable and plays a crucial role in antigen recognition. Profiling the CDR3 regions allows researchers to understand the diversity, clonality, and potential functions of γ/δ T cells in immune responses, including their role in tumor immunosurveillance and immune defense.
While both γ/δ and α/β T cells undergo recombination to form their TCRs, γ/δ T cells are less restricted by major histocompatibility complex (MHC) molecules. This gives them unique antigen recognition properties. Profiling the CDR3 region of γ/δ T cells is distinct because these cells often express more invariant TCRs compared to the highly diverse α/β T cells, which could be key in specialized immune functions like stress surveillance.
TCR γ/δ CDR3 repertoires profiling typically employs high-throughput sequencing technologies, such as next-generation sequencing (NGS), to amplify and sequence the CDR3 regions. Bioinformatics tools are then used to analyze the sequence data, determining clonality, diversity, and specific patterns within the γ/δ TCR repertoires. Computational algorithms aid in assigning TCR genes to sequences.
The CDR3 region is the most variable part of the TCR and is critical for antigen specificity. By profiling the CDR3 region, researchers can identify dominant clonotypes, evaluate the diversity of the γ/δ T cell population, and potentially infer the immune responses these cells are involved in, such as in infections, cancer, and autoimmune conditions.
Clonality refers to the degree to which a few T cell clones dominate the repertoire. A highly clonal repertoire suggests an immune response to a specific antigen, such as in cancer or viral infections, where γ/δ T cells may expand in response to tumor-associated antigens or pathogen-related stress signals. Profiling clonality helps assess the immune system's focus on particular threats.
γ/δ T cells are known for their ability to recognize stress signals in tumor cells, making them key players in cancer immunosurveillance. Profiling their CDR3 repertoires can reveal the presence of tumor-specific or stress-specific TCRs, providing insights into how these cells contribute to natural cancer resistance. This information could be leveraged to develop γ/δ T cell-based immunotherapies.
One challenge in γ/δ TCR profiling is the relatively limited knowledge of γ/δ TCR ligands compared to α/β T cells. Additionally, the low frequency of γ/δ T cells in peripheral blood, technical limitations in distinguishing between functional and non-functional TCR variants, and the complexity of analyzing diverse CDR3 sequences can complicate the profiling process.
Invariant γ/δ TCRs, which have a limited diversity in their CDR3 regions, are crucial for recognizing conserved antigens or stress signals without requiring MHC presentation. Profiling these invariant CDR3 regions provides insight into how γ/δ T cells contribute to rapid immune responses and immunosurveillance, particularly in tissues or during infections and cancer.
TCR γ/δ CDR3 profiling is useful in monitoring immune responses during infections. γ/δ T cells respond to microbial molecules and stress signals from infected cells. By examining their CDR3 repertoires during infections, researchers can assess the extent of γ/δ T cell involvement, identify dominant clones, and better understand their role in pathogen elimination and tissue repair.
By revealing the specific γ/δ TCRs that respond to cancer, infections, or other immune challenges, CDR3 profiling can help identify potential therapeutic targets. γ/δ T cells with unique or invariant TCRs that target tumor or infection-related antigens can be expanded and used in adoptive cell therapies, potentially enhancing the efficacy of immune-based treatments.
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All listed services and products are For Research Use Only. Do Not use in any diagnostic or therapeutic applications.
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