Interaction between insulin receptors and major histocompatibility complex antigens in mouse liver membranes

Insulin receptors from H-2k mouse liver membranes were specifically labelled using a photoreactive insulin analogue coupled to the alpha-subunit (Mr 130,000) of the receptor by ultraviolet-irradiation. Up to 25% of the labelled insulin receptors recovered after membrane solubilization and precipitable by anti-insulin receptor antibodies could be immunoprecipitated by various monoclonal antibodies reacting with H-2Kk antigens. None of these monoclonal antibodies inhibited insulin binding to its receptor. These results show that insulin receptors and H-2Kk antigens interact in liver plasma membranes to form non-covalent complexes. This association between insulin receptors and major histocompatibility complex antigens could be involved in the pathogenesis of certain forms of insulin resistance.