New academic paper: Discovering the Link Between T Cell Receptor Diversity and Herpes Zoster Risk

In a new study led by ImmuneWatch co founders, Prof. Kris Laukens, Prof. Pieter Meysman and Prof. Benson Ogunjimi at the University of Antwerp, researchers have unveiled new insights into how the diversity of T cell receptors (TCRs) influences susceptibility to herpes zoster (HZ), commonly known as shingles. This condition, caused by the reactivation of the varicella-zoster virus (VZV) — the same virus that causes chickenpox — has long puzzled scientists. The study takes a closer look at the role of TCR diversity in combating this virus.

TCR Diversity and Its Impact on VZV

The research team applied a systems immunology approach to examine three distinct cohorts of HZ patients and healthy controls. They focused on the TCR diversity against specific VZV proteins — glycoprotein E (gE) and immediate early 62 and 63 proteins (IE62 and IE63). Their findings revealed that patients who had suffered from HZ exhibited significantly more restricted TCR diversity against VZV gE and VZV IE63 proteins. This was observed particularly in CD4+ T cells after a one-week culture period following stimulation.

Deeper Insights Through Advanced Techniques

The study not only measured TCR diversity but also looked into the activation pathways of these T cells. Utilizing single-cell RNA and TCR sequencing, the researchers identified a marked decrease in T cell activation pathways following stimulation with VZV peptides in patients recovering from HZ. This suggests a reduced functional affinity of TCRs for VZV-specific proteins in these individuals, which may impair their ability to effectively respond to the virus.

Contrasting Findings with Previous Studies

Interestingly, the research contradicts earlier hypotheses that a lower total count of T cells targeting VZV might be a primary factor in HZ susceptibility. Instead, it highlights that neither the total number of VZV-specific CD4+ or CD8+ T cells significantly differed between the HZ patients and the control group.

Implications for Future Research and Vaccine Development

This study is pivotal as it suggests that a lower diversity of CD4+ TCRs, particularly against VZV gE and IE63, might be a risk factor for developing HZ across all age groups. Traditionally, vaccine development has focused on inducing CD8+ T cell responses to protect against viral infections. However, these findings may influence future vaccine strategies to also consider enhancing CD4+ T cell responses as most vaccines aim to increase antibody levels for which CD4+ T cells are needed.

Conclusion

These results provide compelling evidence that TCR diversity is crucial in the body's defense against VZV reactivation and potentially other viral challenges. These insights not only advance our understanding of the immune response to shingles but also open new avenues for therapeutic and preventative strategies against this painful and debilitating condition. As we continue to unravel the complexities of the immune system, studies combining high throughput TCR sequencing and expert immunoinformatic analysis like this are invaluable in guiding us toward more effective health solutions.

Read the paper here:
https://www.cell.com/cell-reports/fulltext/S2211-1247(24)00390-5