Although the predominant repertoire of T cell reactivity to Mtb epitopes is private to individuals, we found striking evidence for population-wide immunodominance at the level of individual pMHC specificity revealed by highly generalisable/public T cell metaclones.

To overcome inter-individual TCR sequence diversity for shared peptide-MHC specific responses to Mtb , we developed a new computational pipeline, Metaclonotypist, to identify HLA-associated clusters of similar TCR sequences (metaclones) across a large ethnically diverse study population.

We used the tuberculin skin test as a standardised in vivo challenge comprising the whole Mtb proteome to generate localised enrichment of Mtb reactive T cells derived from the whole in vivo repertoire, which we characterised by TCR sequencing.

We’re hiring! Looking for a laboratory post-doc fellow to help us disentangle protective and pathogenic T cells in TB, so we can stratify disease-risk after infection, and develop more effective vaccines. Interdisciplinary science in the heart of London. What's not to like? More here: bit.ly/4iIEiwu

and these data from unselected acute respiratory viruses in community acquired infection - with longitudinal sampling after the symptom onset

Not sure if I have misunderstood- our findings that distinct biomarkers discriminate early & late phases of infection were generalisable to all acute respiratory viruses we have been able to test - panel on right = extended time course from Flu challenge

..because of the inherent delay in presentation in naturally acquired infection, upregulation IFI27 achieves higher diagnostic accuracy than other ISG biomarkers for symptomatic infection.

.. another ISG biomarker of viral infection, IFI27 shows later sustained upregulation, subject epigenetic regulation in monocytes

First wave ISGs (eg MX1) induced rapidly, correlate with VL & infectivity - potential biomarker to stratify patients who'll benefit from antivirals?