CELLS EXPRESSING A MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-I MOLECULE WITH A SINGLE COVALENTLY BOUND PEPTIDE ARE HIGHLY IMMUNOGENIC

The major histocompatibility complex (MHC) class I molecules expressed at the cell surface are associated with a large number of different p eptides so that the density of a given MHC-peptide complex is relative ly low. Here we describe the properties of MHC class I molecules genet ically attached to a single antigenic peptide. Cells expressing these fusion proteins are recognized by T cells specific for the particular MHC-peptide complex. Coculture of naive splenocytes with cells express ing these MHC-peptide fusion proteins and the B7.1 antigen allows the induction of primary cytotoxic T lymphocytes (CTL) in vitro. Injection of these cells into naive mice enhances the frequency of specific CTL precursors and protects against a subsequent challenge with a tumor o r a virus bearing the antigenic peptide. Soluble MHC-peptide fusions w ere also produced in which all three components, that is, the heavy ch ain, beta(2)-microglobulin and the peptide, have fused into a single-c hain protein. The availability of MHC class I molecules bound to a sin gle peptide provides valuable tools for the manipulation of CTL respon ses and the analysis of the selection processes in the thymus.