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EBV HORIZONS — Result In Brief

Project ID: 219603
Funded under: FP7-PEOPLE

T lymphocytes in Epstein-Barr infections

The Epstein–Barr virus (EBV) is a virus of the herpes family that causes cancers, immuno-proliferative disorders and acute infectious mononucleosis (AIM). European researchers wish to dissect the immune pathways triggered following EBV infection.
T lymphocytes in Epstein-Barr infections
During viral infections, the immune responses mediated by T lymphocytes are shaped through activation of the T cell receptor (TCR). TCR activation is an instrumental process for immunity and occurs in response to antigen presentation by the relevant cells. T cells that have previously encountered an antigen are known as memory T cells, and upon second encounter with the antigen they are capable of mounting an immune response much faster.

Recent evidence proposes a role for cross-reactive memory T cells in EBV-induced AIM. Working to characterise the precise role of cross-reactive CD8 T cells in the pathology of EBV was the key aim of the EU-funded EBV HORIZONS project. To this end, researchers analysed a panel of EBV-specific CD8 T cell clones from children, adults and elderly individuals with EBV infection. The ultimate goal was to identify the ligands that these clones recognise.

As a first step, researchers analysed the TCR repertoire from healthy individuals of all ages and found many common receptors. The mechanism of convergent recombination was put forward to explain this inter-individual sharing of TCR clonotypes within antigen-specific CD8 T cell populations. According to this mechanism, the shared TCR clonotypes are simply the most frequent products of variable diversity joining (V(D)J) recombination.

The EBV HORIZONS hypothesis was that these shared TCRs may represent clones responsible for the response to infection. By analysing the TCR sequences of the naïve CD8 T cells in mice, scientists found that TCRs with convergent features were present at higher copy numbers within individual mice and were also shared between mice.

Subsequent analysis of naïve and memory T cells in humans revealed that the same mechanism of convergent recombination dictated the TCR repertoire of the naïve and memory CD8 T cell pools, as well as their inter-relationship within and between individuals.

With respect to EBV infection, this information will help unravel the complex immunity against the virus and may be used to modulate immune responses as part of a future therapeutic strategy.

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