Thomas R Müller

Antiviral T cell immunity is primarily orchestrated within tissues, but access to human tissue samples is extremely limited. This creates a major blind spot in our ability to monitor immune responses where viral infections actually occur. Recent studies suggest that some tissue-resident memory T cells (TRM), long thought to be permanently confined to tissues, can re-enter the circulation as ´exTRM´ while retaining distinct tissue-specific imprints. This discovery presents an exciting opportunity: if we can decode these tissue fingerprints, we could use exTRM in blood as indirect proxies for tissue-localized antiviral immunity.This project will systematically characterize exTRM heterogeneity across 25 different viruses, identify tissue-specific signatures by leveraging virus tropism, and validate these findings in human infection cohorts. Using my innovative multiplexed peptide-MHC platform to identify virus-specific T cells in paired blood and tissue samples, I will integrate high-dimensional flow cytometry with multi-omics approaches and novel graph machine learning methods to establish a framework for tracking tissue-imprinted antiviral immune responses through simple blood sampling. This research has significant implications for pandemic preparedness, enabling non-invasive monitoring of tissue-specific immunity to emerging viral threats and providing critical insights for the development of next-generation vaccines that establish robust immunity at viral entry sites.