Cell mediated responses to both viruses and tumors require the presentation of viral or peptide antigens to CD8+ T-cells in the context of molecules encoded by the major histocompatibility complex (class I MHC or MHC I). Normally, this presentation pathway is restricted to endogenously derived antigens which are transported from the cytoplasm to the endoplasmic reticulum (ER) where they assemble with newly formed heterodimeric class I molecules and are then transported to the cell surface. Once on the cell surface, MHC I with bound peptide antigen can engage receptors on the surface of a subpopulation of T-cells which express the accessory molecule CD8, resulting in T-cell activation, and the initiation of a cell mediated immune response. This is distinguished from the MHC class II presentation pathway in which another product of the major histocompatibility complex (class II MHC, or MHC II) acquires exogenous soluble antigens following internalization and proteolytic processing in specialized compartments, and presents these antigens to a different subset of T-cells which display the accessory molecule CD4. As conventional immunization protocols have largely exploited the class II presentation pathway, and therefore stimulation of humoral responses, it would be desirable to develop methodologies to directly load cell surface class I MHC with selected peptides, in order to stimulate cell-mediated immune responses to viruses and tumors without having to use live viruses. The difficulty in doing this lies in our understanding of the structural interactions between the transmembrane heavy chain and beta 2- microglobulin which together make up the class I molecule.
