Human-derived monoclonal autoantibodies as interrogators of cellular proteotypes in the brain

Human-derived monoclonal antibodies (HD-mAbs) can be used to study neural proteotypes, cell populations defined by their proteome rather than their transcriptome.The human antibody repertoire is a nearly inexhaustible source of unique HD-mAbs that can be used to manipulate select proteotypes.Because autoantibodies can cause neuropsychiatric symptoms, some HD-mAbs may help map neural proteotypes to behavioral phenomena.HD-mAbs can traverse the placenta and are easily ported across model systems.Antibody engineering can be used to tune the functional properties of HD-mAbs, thereby increasing their versatility. A major aim of neuroscience is to identify and model the functional properties of neural cells whose dysfunction underlie neuropsychiatric illness. In this article, we propose that human-derived monoclonal autoantibodies (HD-mAbs) are well positioned to selectively target and manipulate neural subpopulations as defined by their protein expression; that is, cellular proteotypes. Recent technical advances allow for efficient cloning of autoantibodies from neuropsychiatric patients. These HD-mAbs can be introduced into animal models to gain biological and pathobiological insights about neural proteotypes of interest. Protein engineering can be used to modify, enhance, silence, or confer new functional properties to native HD-mAbs, thereby enhancing their versatility. Finally, we discuss the challenges and limitations confronting HD-mAbs as experimental research tools for neuroscience. A major aim of neuroscience is to identify and model the functional properties of neural cells whose dysfunction underlie neuropsychiatric illness. In this article, we propose that human-derived monoclonal autoantibodies (HD-mAbs) are well positioned to selectively target and manipulate neural subpopulations as defined by their protein expression; that is, cellular proteotypes. Recent technical advances allow for efficient cloning of autoantibodies from neuropsychiatric patients. These HD-mAbs can be introduced into animal models to gain biological and pathobiological insights about neural proteotypes of interest. Protein engineering can be used to modify, enhance, silence, or confer new functional properties to native HD-mAbs, thereby enhancing their versatility. Finally, we discuss the challenges and limitations confronting HD-mAbs as experimental research tools for neuroscience.