Induction of anergy in human T lymphocytes by exposure to single amino acid mutated antigens

Abstract

Anergy is a condition of immune T cells becoming sustainably inactive. Theoretically, it occurs when a T cell recognizes its antigen but cannot be active. If we could artificially induce anergy to a specific T cell clone, this should provide a therapeutic strategy for autoimmune disease. One possible method to induce anergy is to expose a T cell to an unstably presented antigen, which makes the T cell bind to the antigen but not become active due to insufficient duration of antigen presentation. The present study attempted to realize this condition in human T lymphocytes by single amino acid mutation of the antigen. As a result, the potentiality of this method for anergy-induction in human T lymphocytes was revealed. By in silico protein structure prediction, it was suggested that optimal range of contact energy between the antigen and the major histocompatibility complex was required for successful induction. From the gene expression profile, emergence of CD4+/TSHZ2+ T cell population was suggested as one of the hallmarks of anergy-induction by this method. This was the first study to demonstrate anergy-induction by the destabilized antigen strategy in human cells.