Antigen identification for HLA class I- and HLA class II-restricted T cell receptors using cytokine-capturing antigen-presenting cells.

ABSTRACT: A major limitation to understanding the associations of human leukocyte antigen (HLA) and CD8⁺ and CD4⁺ T cell receptor (TCR) genes with disease pathophysiology is the technological barrier of identifying which HLA molecules, epitopes, and TCRs form functional complexes. Here, we present a high-throughput epitope identification system that combines capture of T cell-secreted cytokines by barcoded antigen-presenting cells (APCs), cell sorting, and next-generation sequencing to identify class I- and class II-restricted epitopes starting from highly complex peptide-encoding oligonucleotide pools. We engineered APCs to express anti-cytokine antibodies, a library of DNA-encoded peptides, and multiple HLA class I or II molecules. We demonstrate that these engineered APCs li

SUBMITTER: Lee MN 

PROVIDER: S-EPMC8320540 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature