SINGLE-CHAIN MHC CLASS-II MOLECULES INDUCE T-CELL ACTIVATION AND APOPTOSIS

MHC class II/peptide complexes displayed on the surface of APCs play a pivotal role in initiating specific T cell responses, Evidence is pre sented here that components of this heterotrimeric complex can be gene tically linked into a single polypeptide chain, Soluble single-chain ( sc) murine class II IA(d) molecules with and without covalently attach ed peptides were produced in a recombinant baculovirus-insect cell exp ression system, Correct conformation of these molecules was verified b ased on 1) reactivity to Abs directed against conformational epitopes in IA(d) and 2) peptide-specific recognition of the IA(d)/peptide comp lexes by T cells, Both sc class II molecules loaded the appropriate pe ptides and sc class II/peptide fusions were effective in stimulating T cell responses, including cytokine release and apoptosis. Mammalian c ells were also found to be capable of expressing functional sc class I I molecules on their cell surfaces, The findings reported here open up the possibility of producing large amounts of stable sc class II/pept ide fusion molecules for structural characterization and immunotherape utic applications.