A Divalent Major Histocompatibility Complex/IgG1 Fusion Protein Induces Antigen-Specific T Cell Activationin Vitroandin Vivo

Activation of antigen-specific T cell clonesin vivomight be possible by generating soluble MHC molecules; however, such molecules do not induce effective T cell responses unless cross-linked. As a first step in generating a soluble MHC molecule that could function as an antigen-specific immunostimulant, the extracellular domains of the murine H-2KbMHC class I molecule were fused to the constant domains of a murine IgG1 heavy chain, resulting in a divalent molecule with both a TCR-reactive and an Fc receptor (FcR)-reactive moiety. The fusion protein can be loaded with peptide and can induce T cell activation in a peptide-specific, MHC-restricted manner following immobilization on plastic wells or following cross-linking by FcR+spleen cells. The fusion protein induces partial T cell activationin vivoin a mouse transgenic for a TCR restricted to H-2Kb. This fusion protein molecule may be useful to study peptide–MHC interactions and may provide a strategy for boostingin vivoantigen-specific T cell responses, such as to viral or tumor antigens.