Effects of human monoclonal anti-GluN1 autoantibodies on NMDA receptor channel function
In autoimmune encephalitis, intermediate and long-term autoantibody effects on synaptic target antigen have been described, e.g. for the NMDA receptor (NMDAR). Here, we focus on investigating direct effects of specific monoclonal human autoantibodies against the GluN1 subunit of the NMDAR possibly contributing to disease-relevant receptor and neuronal dysfunction. We will use fast application techniques to outside-out patches to evaluate effects of pathogenic antibodies on kinetics of average currents. These macroscopic effects of selected clones of anti-GluN1 antibodies will then be classified more precisely by single channel recording to reveal information on channel open probabilities and fine structure of NMDAR channel kinetics. Furthermore, we will test modified IgG antibodies, e.g. with genetically encoded labels and Fab fragments to investigate their binding and effects on the NMDA receptor.