Analyzing the Binding Interactions of Major  Histocompatibility Complex Class I at Neuronal Synapses

Kim, Hyunjean Catherine [Browse]
Senior thesis
95 pages


Boulanger, Lisa [Browse]
Princeton University. Department of Molecular Biology [Browse]
Class year
Summary note
Although MHC class I has been well classified in the immune system as a class of antigen presenters, recent investigations have revealed a non- immune functions for these proteins in the brain. Hippocampal neurons that are deficient in cell-surface MHC class I have increased NMDAR-mediated currents, demonstrating a regulatory role of MHC class I. To explore the molecular mechanism by which MHC class I regulates NMDARs, this thesis investigated the binding interactions of MHC class I molecules with candidate binding partners spinophilin and PSD-95. Specifically, the intracellular domains of MHC class I proteins were studied by cloning the cytoplasmic tails into vectors for use in co-immunoprecipitation, overlay assays, and pull-down assays. Recombinant cytoplasmic tails of non-classical MHC class I protein T22 did not pull down endogenous PSD-95, although they did bind the recombinant PDZ domains of PSD-95. Due to experimental errors, the co-immunoprecipitation of classical MHC class I K recombinant cytoplasmic tails with hippocampal lysates was not conclusive. The results of this thesis suggest that T22 does not bind PSD-95. The regulatory role of MHC class I on NMDARs could contribute to NMDAR dysfunction in brain disorders, such as schizophrenia.

Supplementary Information