The major histocompatibility complex class I heavy chain as a structural subunit of the human cell membrane insulin receptor: implications for the range of biological functions of histocompatibility antigens.
Monoclonal antibodies against some of the monomorphic determinants of major histocompatibility complex (MHC) class I molecules reduce insulin binding and precipitate 125I-labeled insulin receptor preparations. A monoclonal antibody with specificity for the insulin binding site on the cell membrane insulin receptor of human cells was used to precipitate insulin receptors from human cell lines and resulted in distinct bands of Mr approximately 130,000, 90,000, and 45,000. The Mr 45,000 molecules thus precipitated were subjected to NaDodSO4/PAGE, eluted from the gels, and found to react with monoclonal antibodies against monomorphic and a polymorphic MHC class I determinant known to be expressed on the cell line used as receptor source. Moreover, a murine thymoma line (RI) with MHC class I expression bound significant amounts of insulin, whereas a MHC class I-negative variant had low insulin binding capacity. Reduction in the density on human cells of the MHC class I heavy chain was obtained by capping with antibodies to beta 2-microglobulin or to the MHC class I heavy chain and resulted in decreased insulin binding, whereas down-regulation of insulin receptors induced increased density of MHC class I molecules. It is concluded that the MHC class I heavy chain and the tetrameric insulin receptor are structurally associated in the cell membrane and suggested that this association may occur by displacement of beta 2-microglobulin by the insulin receptor.
D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D005260:Female; D006649:Histocompatibility Antigens / Q000276:immunology*; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007328:Insulin / Q000031:analogs & derivatives / Q000378:metabolism; D008285:Major Histocompatibility Complex; D010920:Placenta / Q000378:metabolism; D011247:Pregnancy; D011972:Receptor, Insulin / Q000235:genetics*
D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D006649:Histocompatibility Antigens; D007143:Immunoglobulin Heavy Chains; D007328:Insulin; C008147:insulin, iodo-; D011972:Receptor, Insulin