Inhibitors of T-cell activation

A method of tolerizing a T-cell to an antigen, comprising contacting said T-cell with an antigen-presenting cell which is presenting a peptide derived from said antigen complexed to a MHC molecule and a bispecific fusion protein comprising a ligand specific for CTLA-4 and a ligand specific for a peptide-MHC class II (pMHCII) complex, wherein the T-cell expresses a T-cell receptor (TCR) and cell surface CTLA-4, and the ligand specific for CTLA-4 is selected from the group consisting of CD80 (B7-1), CD86 (B7-2), and mutants thereof with greater binding avidity for CTLA-4 than CD28, thereby crosslinking CTLA-4 to the pMHCII complex and the TCR.