Structure and function of a membrane-bound murine MHC class I molecule

MHC molecules are expressed at the surface of nucleated cells to present pe ptides to T cells. Structural information on MHC molecules has been gathere d by x-ray crystallography techniques by using soluble proteins. Although r elationships between MHC molecules and cell membranes have not been studied in detail, they are of critical importance for T cell recognition. Using a chemically modified lipid, we have been able to capture and orient histidi ne-tagged MHC molecules on lipid membranes. Surface plasmon resonance exper iments show that the protein binds to the nickel lipid in a specific manner and in an oriented fashion, which allows T cell receptor binding. Similar lipid surfaces have been used to gravy two-dimensional crystals and to dete rmine the structure of a membrane-anchored murine H-2K(b) MHC class I molec ule. The docking of the crystallographic structure into the three-dimension al reconstructed Structure derived from the two-dimensional crystals allows us to determine that the histidine tag is near the membrane surface and th at the MHC molecule is in an upright position, exposing the peptide/alpha 1 -alpha 2 domains toward the T cell.