Our immunology group's current interest is in development of recombinant single chain MHC molecules in order to study their cell biology, immune function, potential use as vaccine components and as tools for studying T cell repertoire selection. This is an outgrowth of our long standing interest in immunochemical methods for cell separation, and in developing engineered macromolecular reagents for use as potential anticancer immunogens, and for study of relatively low affinity interactions (such as those of MHC molecules with peptides and T cell receptors). Class I MHC molecules primarily bind peptides from endogenously synthesized proteins, and infected cells display pathogen peptides on their surfaces as MHC - peptide complexes. The recognition of these complexes by the specific receptors of CD8+ T cells has been implicated in immune responses to cancers such as melanoma. This recognition is also an important component of antiviral immune responses, including resistance to HIV. Our recombinant single chain class I MHC molecules, unlike the wild type two chain molecules, have a non-dissociable beta2 microglobulin domain. In further studies of her recombinant human single chain HLA-A2.1 molecule, Dr. Li Lee has found that it is functional in binding and presentation of an HTLV-I peptide to the appropriate human T cells. Class II MHC molecules primarily bind peptides from exogenous proteins and present them to the CD4+ T cells that act as helper cells for antibody production and modulate other T cell responses through their secretion of cytokines. During this year, Dr. Jill Zhu has extended our studies by synthesizing and expressing recombinant human class II MHC molecules (HLA-DR and DQ) with covalently attached viral peptides from influenza and HIV.
