MHC molecules are proteins that sit on the surface of cells in the human body. If the cells are infected, or if they become cancerous, the MHC molecules capture and display pieces (peptides) from the proteins of the infecting organisms or the cancer cells. These displayed pieces can then be recognized by certain white blood cells called T lymphocytes. Under the right circumstances this T cell recognition can lead to an immune reaction against the infection or cancer, or to inhibition or potentiation of unwanted autoimmune responses. We construct recombinant single chain MHC molecules in order to study their cell biology, immune function, potential use as vaccine components, and to help learn how T cell populations develop that can recognize many different peptides. Class I MHC molecules on infected or cancerous cells display peptides from within these cells. Recognition of these peptides by CD8 T cells contributes to immune responses to cancers such as melanoma, and to antiviral immune responses, including resistance to HIV. In nature, the Class I molecules are formed of three components that can slowly fall apart. This limits the time during which an immune reaction can occur. We have prepared a soluble class I HLA-A2.1 molecule with a covalent TAX peptide from HTLVI for use as a potential inhibitor of autoimmune tropical spastic paralysis, and an HLA-A2.1 molecule with a covalent MART1 melanoma peptide, to study the T cell response to this peptide.Class II MHC molecules on CD4 T cells bind peptides from foreign proteins that are engulfed and fragmented. The CD4 T cells act as helpers for antibody production. They also increase or inhibit other T cell responses by secreting local hormones called cytokines. During this year, Dr. Xiaojie Zhu (who tragically died of cancer last September) engineered monomeric and oligomeric single chain Class II MHC (HLA-DR) molecules with covalent agonist and antagonist peptides to study signaling through the T cell receptor, and for use as potential immunogens and inhibitors. During the past year we have produced and purified these recombinant MHC molecules use in such studies. We have also studied the relative degradation of oligomeric surface Class II MHC molecules in cells withdifferent expression pathways. - AIDS, cancer immunotherapy, MHC Class I, MHC Class II, Vaccines, MHC Oligomers, Antagonists, - Neither Human Subjects nor Human Tissues
