Hepatitis C virus-cross-reactive TCR gene-modified T cells: a model for immunotherapy against diseases with genomic instability.

摘要: A major obstacle hindering the development of effective immunity against viral infections, their associated disease, and certain cancers is inherent genomic instability. Accumulation mutations can alter processing presentation antigens recognized by antibodies T cells that lead to immune escape variants. Use an agent intrinsically combat rapidly mutating or cancer-associated would be quite advantageous in developing such disease. We propose harboring cross-reactive TCRs could serve as a therapeutic these instances. With use hepatitis C virus, known for its instability model mutated antigen recognition, we demonstrate cross-reactivity immunogenic mutagenic nonstructural protein 3:1406-1415 3:1073-1081 epitopes PBL-derived, TCR-gene-modified cells. These single TCR-engineered CD8-independently recognize naturally occurring epidemiologically relevant mutant TCR-peptide MHC modeling data allow us rationalize how TCR structural properties accommodate recognition substitutions impact requirement CD8 affinity enhancement recognition. better understanding TCRs' promiscuous behavior may exploitation develop novel, adoptive cell-based therapies infections exhibiting similar