Possibly one of the most important studies on EBV and human immunity in a long time.
It shows that a special type of immune cell - γδ T cells (Vδ1) - can detect and destroy EBV-infected cells even when the virus hides from the classical immune system.🧵
It shows that a special type of immune cell - γδ T cells (Vδ1) - can detect and destroy EBV-infected cells even when the virus hides from the classical immune system.🧵
https://twitter.com/atranscendedman/status/1977353205710307470
The team used a human blood infection model and single-cell RNA sequencing to map every immune response to EBV.
This unbiased approach revealed players that traditional assays often miss - including the elusive γδ T cells.
This unbiased approach revealed players that traditional assays often miss - including the elusive γδ T cells.
In healthy people, EBV control relies on teamwork
CD8 T cells and NK cells handle direct killing,
but γδ T cells (Vδ1) join the fight as a third, previously underappreciated line of defense.
CD8 T cells and NK cells handle direct killing,
but γδ T cells (Vδ1) join the fight as a third, previously underappreciated line of defense.
These Vδ1 cells work differently.
They don’t need the virus to be presented via HLA molecules.
Instead, they recognize stress signals on infected cells - markers like MICA, CD155, or B7-H6 that basically say, something’s wrong here.
They don’t need the virus to be presented via HLA molecules.
Instead, they recognize stress signals on infected cells - markers like MICA, CD155, or B7-H6 that basically say, something’s wrong here.
That lets them attack viruses that can otherwise hide.
Once activated, Vδ1 cells turn into so-called DOT cells (Delta One T).
They’re packed with cytotoxic weapons like perforin and granzymes - enzymes that literally punch holes in infected cells.
In lab tests, they efficiently killed EBV-positive cell lines.
They’re packed with cytotoxic weapons like perforin and granzymes - enzymes that literally punch holes in infected cells.
In lab tests, they efficiently killed EBV-positive cell lines.
In a mouse model of EBV-related cancer, Vδ1 cells migrated straight into the tumor, became activated, and slowed tumor growth.
Not a cure yet - but a clear biological signal that this immune pathway could be harnessed therapeutically.
Not a cure yet - but a clear biological signal that this immune pathway could be harnessed therapeutically.
Why it matters.
EBV is linked to certain cancers and autoimmune diseases.
Vδ1 T cells could offer a new way to target infected or malignant cells that evade classical immune recognition - and they could be made off the shelf, usable for any patient.
EBV is linked to certain cancers and autoimmune diseases.
Vδ1 T cells could offer a new way to target infected or malignant cells that evade classical immune recognition - and they could be made off the shelf, usable for any patient.
Immunity has more layers than we thought.
Beyond antibodies and conventional T cells, there are backup systems that detect cellular stress rather than specific viral fragments.
Those ancient pathways might be the key to controlling persistent viruses like EBV!
Beyond antibodies and conventional T cells, there are backup systems that detect cellular stress rather than specific viral fragments.
Those ancient pathways might be the key to controlling persistent viruses like EBV!
Sum:
EBV control = cellular immunity, not antibodies.
Vδ1 γδ T cells kill infected cells without HLA.
A new path toward broad, universal cell-based therapies.
EBV control = cellular immunity, not antibodies.
Vδ1 γδ T cells kill infected cells without HLA.
A new path toward broad, universal cell-based therapies.
Jiménes at al., A high-resolution, unbiased analysis of the cellular immune response to Epstein-Barr virus. biorxiv.org/content/10.110…
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