Class I histocompatibility (MHC) antigens are integral membrane glycoproteins expressed on the surfaces of all mammalian somatic cells. These molecules present foreign antigen to T lymphocytes, thereby regulating cellular immune responses. An area of intense study is the elucidation of the mechanism for the formation of the class I MHC- antigenic peptide-b2-m complex and for transporting it to the cell surface. A second important issue is the fate of cells surface class I MHC molecular after it has lost antigenic peptide and b2-microglobulin light chain. It is important to understand these mechanisms, since intracellular trafficking surely plays an important role in the functions of these molecules during immunosurveillance. For example, Class I MHC antigens acquire the antigenic peptides which they present to T lymphocytes (e.g., tumor and viral antigens) within the cell in which both the MHC antigen and the immunogenic antigen are synthesized. Acquisition of antigenic peptide is required for efficient transport of the class I MHC molecule to the cell surface. A detailed understanding of these mechanisms may lead to the development of better vaccines and of more effective means of treating cancers and autoimmune diseases. The major goal of this research project is to elucidate basic mechanisms in the assembly of the class I MHC molecule with antigenic peptide and b2-m during biosynthesis, the transport of this complex through the cell, and its fate once at the cell surface. To attain this goal we are using specific antibodies which detect assembled and disassembled class I MHC molecules in cell biological and biochemical experiments on normal and mutant cell lines defective in assemble and/or transport of class I MHC molecules. MBRS students will be involved in all phases of this project.
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