Search results for "T cell repertoire"
showing 4 items of 4 documents
Identification of a tumor-reactive T-cell repertoire in the immune infiltrate of patients with resectable pancreatic ductal adenocarcinoma
2016
The devastating prognosis of patients with resectable pancreatic ductal adenocarcinoma (PDA) presents an urgent need for the development of therapeutic strategies targeting disseminated tumor cells. Until now, T-cell therapy has been scarcely pursued in PDA, due to the prevailing view that it represents a poorly immunogenic tumor.We systematically analyzed T-cell infiltrates in tumor biopsies from 127 patients with resectable PDA by means of immunohistochemistry, flow cytometry, T-cell receptor (TCR) deep-sequencing and functional analysis ofProminent T-cell infiltrates, as well as tertiary lymphoid structures harboring proliferating T-cells, were detected in the vast majority of biopsies f…
Immunosenescence and anti-immunosenescence therapies: the case of probiotics.
2008
ABSTRACT Aging is a complex process that negatively impacts the development of the immune system and its ability to function. Progressive changes in the T and B cell systems over the life span have a major impact on the capacity to respond to immune challenge. These cumulative age-associated changes in immune competence are termed immunosenescence. This process is mostly characterized by: (1) shrinkage of the T cell repertoire and accumulation of oligoclonal expansions of memory/effector cells directed toward ubiquitary infectious agents; (2) involution of the thymus and the exhaustion of naive T cells; and (3) chronic inflammatory status. Here we discuss possible strategies to counteract t…
Proteasomes shape the repertoire of T cells participating in antigen-specific immune responses
2006
Differences in the cleavage specificities of constitutive proteasomes and immunoproteasomes significantly affect the generation of MHC class I ligands and therefore the activation of CD8-positive T cells. Based on these findings, we investigated whether proteasomal specificity also influences CD8-positive T cells during thymic selection by peptides derived from self proteins. We find that one of the self peptides responsible for positive selection of ovalbumin-specific OT-1 T cells, which is derived from the f-actin capping protein (Cpalpha1), is efficiently generated only by immunoproteasomes. Furthermore, OT-1 mice backcrossed onto low molecular mass protein 7 (LMP7)-deficient mice show a…
Prediction of Specific TCR-Peptide Binding From Large Dictionaries of TCR-Peptide Pairs
2019
Abstract The T cell repertoire is composed of T cell receptors (TCR) selected by their cognate MHC-peptides and naive TCR that do not bind known peptides. While the task of distinguishing a peptide-binding TCR from a naive TCR unlikely to bind any peptide can be performed using sequence motifs, distinguishing between TCRs binding different peptides requires more advanced methods. Such a prediction is the key for using TCR repertoires as disease-specific biomarkers. We here used large scale TCR-peptide dictionaries with state-of-the-art natural language processing (NLP) methods to produce ERGO (pEptide tcR matchinG predictiOn), a highly specific classifier to predict which TCR binds to which…