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MR1T cells, a novel population of MR1-restricted T cells
Third-party funded project
Project title MR1T cells, a novel population of MR1-restricted T cells
Principal Investigator(s) De Libero, Gennaro
Project Members Pereira Loureiro, Jose Pedro
Spagnuolo, Julian
Yang, Qinmei
Schäfer, Verena
Organisation / Research unit Departement Biomedizin / Experimental Immunology (De Libero),
Bereich Medizinische Fächer (Klinik) / Tumorimmunologie (De Libero)
Project start 01.05.2020
Probable end 30.04.2023
Status Completed
Abstract

MR1 is a MHC class-I-like molecule that presents small antigens to T cells. Vitamin B2-related metabolites produced by some bacteria were initially identified as MR1-presented antigens. Recently, we identified a novel population of human T cells that are restricted to MR1 and do not recognize microbial metabolites (called MR1T cells). We found that MR1T cells recognize MR1 molecules presenting self-metabolites that accumulate in tumors, and not in normal cells, upon metabolic alterations of some metabolic pathways. These preliminary results are the basis for the studies proposed here. The main objectives of these studies are a further understanding of the nature of MR1-presented molecules and their structure, as well as the characterization of MR1T cell subpopulations and their immunological functions.The aims of the proposed studies are:1.Investigation of the repertoire of MR1-binding ligands. These studies will be performed by using four types of assays to identify scaffold molecules binding MR1.2.Isolation and characterization of MR1T cells.This goal will be achieved by performing single-cell transcriptome analysis of freshly isolated MR1T cells using antigen-loaded MR1 tetramers and by analyzing the MR1T cell TCR repertoire, using a novel approach.3.Identification of MR1T cell antigensThis goal will be accomplished by making genomic screen for biosynthetic pathways promoting MR1T recognition and by purification of MR1T antigens followed by structural elucidation using LC-MS-MS.Understanding the immunological role of MR1T cells and the structural features of MR1-binding molecules will unveil how T cells survey the metabolic integrity of other cells, an unprecedented homeostatic function of the immune system.

Financed by Swiss National Science Foundation (SNSF)
   

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29/03/2024