Figure 1.

Altering the peptide ligand at the immunologic synapse elicits an effector T cell response to a self-antigen. (A) Self-antigens are displayed as peptides bound to MHC on professional APC but because of the low avidity of the T cell repertoire, insufficient signaling is generated to induce an effector T cell response and tumor cells expressing the self-antigen are ignored. (B) Altering amino acid residues of the peptide that protrude out from the MHC molecule and contact the T cell receptor (TcR) improves the affinity of the interaction and promotes signaling and T cell activation. The result is expansion of self-reactive T cells and differentiation to effector cells that have a lower threshold for activation and recognize tumor cells expressing the native self-peptide.