Tu185 - Ecoclusters: A Growing Catalog of Humanity’s Collective T Cell Responses to Prevalent Immune Exposures

Abstract Text: A subset of T-cell receptors (TCRs) in a typical immune repertoire are present in many individuals exposed to the same immune exposure (e.g., virus). Previously (https://www.biorxiv.org/content/10.1101/2024.03.26.583354v1), we have used our database of tens of thousands of T-cell repertoires to discover many groups of TCRs (called ECOclusters) that co-occur in the same people. We've shown that ECOclusters represent public T-cell responses to a prevalent immune exposures by demonstrating that several ECOclusters comprise strong diagnostic markers for their associated exposures (SARS-CoV-2, CMV, EBV, HSV-1, HSV-2, Parvovirus and T. gondii).

Here, we greatly expand our catalog of ECOcluster-disease associations in two ways: we've used our in-house MIRA assay to determine the antigen specificity of thousands of ECOcluster TCRs; and we've performed Adaptive Immunosequencing on hundreds of blood samples that have also undergone Infinity Bio's VirSIGHT assay, providing scores for the serological response of each donor to hundreds of viral pathogens. The result is a growing catalog of dozens of ECOclusters associated with the prevalent pathogens they respond to. These ECOclusters can provide diagnostic markers of exposure, and they can also describe the extent of a given individual's T-cell response to a disease and their time since exposure.

Further, substructure within the ECOcluster associated with EBV reveals different subgroups of people who respond in different ways, with some subclusters diminishing over time and others remaining throughout the person's life.

ECOclusters are an increasingly powerful tool for describing a person's immune history and gaining insights into the different ways people respond to disease.