ENAapplication/xmlftp://primaryOK200GenomicsSchober Lab, Mikrobiologisches Institut - Klinische Mikrobiologie, Immunologie und Hygiene, Friedrich-Alexander-Universität Erlangen-Nürnberghttps://www.ebi.ac.uk/ena/browser/view/PRJNA843995Homo sapiensT cell receptor (TCR) avidity is assumed to be a major determinant of the spatiotemporal fate and protective capacity of tumor-specific T cells. However, monitoring polyclonal T cell responses with known TCR avidities in vivo over space and time remains challenging. Here, we investigated the fate and functionality of tumor neoantigen-specific T cells with TCRs of distinct avidities in a well-established, reductionist preclinical tumor model and human melanoma patients. Surprisingly, we found that both high- and low-avidity T cells are similarly abundant within the tumor and adopt concordant phenotypic signs of exhaustion. Outside the tumor, high-avidity TCR T cells were also not generally overrepresented, but instead selectively enriched in T cell populations with intermediate PD-1 protein expression or corresponding RNA and surface protein signatures of recent activation. Tumor-reactive TCRs with high protective capacity circulating in peripheral blood are therefore characterized by a signature of recent activation. Overall design: scRNA sequencing data for antigen specific cells before and after TIL infusion and from the infusion product of melanoma patientsxref:PubMed:35960818ENAfalseSignatures of recent activation identify a circulating T cell compartment containing tumor-specific antigen receptors with high aviditySignatures of recent activation identify a circulating T cell compartment containing tumor-specific antigen receptors with high avidity2025-09-242022-06-04PRJNA843995GSE205145960635960818