Novel costimulatory fusion proteins and DNA sequences that enhance T cell responses to weakly immunogenic and/or lowly expressed antigens and that confer T cell resistance against MDSC-mediated suppression are disclosed. The fusion proteins comprise portions of CD4, CD8α or the T cell receptor linked to a specific region of MyD88 or other signaling molecules. These fusion proteins and sequence variants thereof improve T cell activation and responsiveness. Also disclosed is the use of these molecules in host cells as a means to enhance and costimulate responses of immune cells including cytotoxic CD8+ T cells and the use of these cells to treat cancer, infectious agents and other diseases.
