TCR Clonality Assessment Service

Introduction to TCR Clonality Assessment

T-cell receptor (TCR) clonality assessment offers significant value in both clinical settings and research. Each T cell normally carries a unique TCR under healthy conditions. These receptors can recognize different antigens. This creates a highly diverse TCR repertoire in the body. Disease changes this pattern dramatically. One or a few T cell clones start to multiply rapidly during illness. This pathological expansion shows specific characteristics. The TCR repertoire becomes dominated by single clones or a few clones. Diversity drops significantly. These changes work as important molecular markers. Doctors use them for diagnosis, monitoring, and predicting outcomes. Clinically, TCR clonality tracking helps in multiple ways. It allows patient stratification based on immune profiles. It predicts how patients might respond to treatment. It monitors minimal residual disease (MRD) levels. It also measures how well immunotherapies are working.

At Creative Biolabs, we provide specific and reliable measurements of clonal diversity in T cell populations. Through this assessment, researchers can detect dynamic biomarkers across many diseases and understand the current state of the immune system.

Overview of TCR Biology: The Foundation of Diversity

TCR is a membrane protein made of two different chains. Most circulating T cells (90%-99%) carry receptors with α and β chains. The γ/δ types prefer epithelial tissues. The main job of αβ TCRs is recognizing foreign peptides alongside major histocompatibility complex (MHC) molecules.

The huge diversity of TCR repertoires forms the backbone of adaptive immunity. This diversity lets our immune system recognize almost unlimited numbers of antigens. The diversity comes from T-cell development in the thymus. During this process, genes rearrange through V(D)J recombination.

How Diversity Forms

Gene segments combine during development. V (variable) and J (joining) segments create the variable part of the α chain. The β chain needs three segments: V, J, and D.

In mice, there are roughly 100 V and 60 J segments for α chains. For β chains, there are 35 V, 12 J, and 2 D segments. But about one-third of these don't work properly.

The most important part for antigen recognition is CDR3. This region recognizes the peptide-MHC complex. CDR3 sits at the V(D)J junction. Random nucleotides get added or removed between segments here. This creates even more diversity beyond what comes from basic recombination¹.

Each new T cell gets a potentially unique receptor. This creates an extremely diverse TCR collection.

Shaping the Final Repertoire

The thymus refines this diversity during T-cell maturation. Two selection processes occur here. Positive selection ensures MHC restriction. Negative selection creates central tolerance. Both processes are essential for proper T-cell function.

Scientists still debate the exact size of human αβ TCR repertoires. Estimates range from 25 million to 100 million unique receptors. In house mice, researchers found about 1.9 million unique TCR αβ combinations. The number of unique TCRβ chains reaches 500,000 to 800,000 different types¹.

Figure 1 Schematic representation of the TCRβ chain rearrangement ²

When Things Go Wrong

Disease changes this normal pattern. Chronic infections, cancer, or autoimmune conditions create persistent antigen exposure. This leads to sustained, large-scale expansions of specific clones. The balanced repertoire shifts toward oligoclonality, where just a few clones dominate.

T-cell cancers represent the extreme case. A single transformed cell grows uncontrollably, creating a monoclonal population that crowds out normal diversity.

Private vs. Public Clones

These expanded clones fall into two categories:

Private clones are unique to each person. They reflect individual immune histories and genetic backgrounds.

Public clones appear across different people. These clones often share identical or very similar CDR3 sequences. They typically develop in response to common pathogens that many people encounter.

Understanding whether clones are private or public helps researchers interpret immune responses and disease patterns across populations.

Methods and Workflow

Researchers have several ways to measure TCR clonality. The methods got much better over time. You pick one based on what you need to find out, how sensitive the test needs to be, what samples you have, your budget, and how fast you need answers.

How Different Methods Work

Picking the Right Method

What you choose depends on your situation:

Need quick answers? Flow cytometry works great

Want proven methods? BIOMED-2 PCR is reliable

Need detailed information? NGS tells you everything

Working outside the lab? Nanopore travels well

Tight budget? Spectratyping costs least (but barely works anymore)

What We Offer

Complete TCR Clonality Workflow

Novel Method Development

Clinical Applications

Applications of TCR Clonality Assessment

Researchers now rely on TCR clonality measurements for both patient care and research. This technique has found uses in many medical areas.

Diagnosis and Prognosis

Blood cancers, particularly T-cell lymphomas, show a clear pattern. A single dominant TCR clone appears when the disease develops. This finding helps doctors confirm their diagnosis. NGS changed everything. Traditional PCR methods could only detect 44-72% of cutaneous T-cell lymphoma cases. NGS now catches 69-100% of them. Doctors combine TCR data with genetic mutations. This combination helps them predict how patients will respond to treatment. The approach works best in early mycosis fungoides cases.

Tracking MRD

NGS-based TCR sequencing detects cancer cells at extremely low levels. It can find one cancer cell among 100,000 healthy ones. Flow cytometry can only detect one in 1,000 to 10,000 cells. This sensitivity matters in AML. Doctors spot returning cancer much earlier. Early detection creates more treatment options.

Monitoring Immunotherapy Response

TCR analysis shows whether immunotherapy is working. Successful treatments cause specific T-cell clones to multiply rapidly. This expansion often happens before patients show clinical improvement. HPV16-driven cancers provide a clear example. Patients who developed dominant TCR clones after chemoradiation achieved complete remission. This discovery led to "TCR-focused" therapies. Doctors now identify each patient's most effective anti-tumor TCRs. They use these TCRs to create personalized cell treatments.

Autoimmune Diseases

TCR sequencing identifies the T-cell clones that attack healthy tissue. For example, in Lupus Nephritis, scientists found overactive PD-1⁺ CD8⁺ T-cell clones in inflamed kidneys. PD-1 pathway drugs might help these patients. In Primary Sjögren's Syndrome, researchers discovered GZMK⁺ CXCR6⁺ CD8⁺ T-cells in both blood and salivary glands. More of these cells means worse disease. IL-15 pathway treatments show promise. Among Autoimmune Hemolytic Anemia, patients with clonal T-cell populations get sicker. They also take longer to respond to treatment.

Transplant Medicine

Some bone marrow transplant patients develop dangerously low blood counts. Large-granular lymphocytosis causes this problem. TCR analysis proves that clonal T-cell expansion drives the condition in nearly half of cases. These finding changes treatment decisions. Doctors use immunosuppressive drugs to solve the problem. The treatment works well.

Infectious Diseases

TCR analysis reveals how our immune system fights infections and responds to vaccines. In Chronic Viral Infections: Viruses like Cytomegalovirus permanently alter our TCR patterns. They create lasting, oligoclonal signatures that researchers can track for over ten years. Among COVID-19 Research, scientists compared mRNA vaccination to natural infection using TCR sequencing. The immune responses differ in timing and strength. T-cell clones expand and shrink at different rates. This information helps design better booster strategies. The technique also tracks SARS-CoV-2-specific memory T-cells over time. Vaccination creates immune protection that lasts.

Clinical Impact

TCR clonality assessment moved from research labs to hospital bedrooms. It now helps diagnose diseases and predict outcomes. Doctors use it to monitor treatments and design personalized therapies. The technique works across many medical specialties.

Our Advantages

Technical Excellence

We deliver results faster than most competitors in the market. Our testing maintains high accuracy standards with built-in quality guarantees. You don't need to worry about sample handling or data processing. We manage the entire workflow from sample receipt to final report delivery. This complete service approach saves you time and reduces potential errors.

Beyond Basic Testing

We offer custom bioinformatics analysis tailored to your specific research questions. Our team provides clinical trial support to help you meet regulatory requirements. We host free technical training sessions at academic conferences. You can also get publication support when you need help analyzing data for research papers. These extra services make us more than just a testing lab.

Our team handles the complex technical work so you can focus on patient care and research. We deliver reliable results quickly with the support you need.

FAQ

References

1. Kansal R. "Is It Time to Assess T Cell Clonality by Next-Generation Sequencing in Mature T Cell Lymphoid Neoplasms? A Scoping Review". Journal of Molecular Pathology. vol. 6,1 2025, https://doi.org/10.3390/jmp6010002
2. Migalska, Magdalena et al. “Profiling of the TCRβ repertoire in non-model species using high-throughput sequencing.” Scientific reports vol. 8,1 11613. 2 Aug. 2018, https://doi.org/10.1038/s41598-018-30037-0
3. Distributed under Open Access license CC BY 4.0, without modification.