Understanding the focused CD4 T cell response to antigen and pathogenic organisms.

Immunodominance is a term that reflects the final, very limited peptide specificity of T cells that are elicited during an immune response. Recent experiments in our laboratory compel us to propose a new paradigm for the control of immunodominance in CD4 T cell responses, stating that immunodominance is peptide-intrinsic and is dictated by the off-rate of peptides from MHC class II molecules. Our studies have revealed that persistence of peptide:class II complexes both predicts and controls CD4 T cell immunodominance and that this parameter can be rationally manipulated to either promote or eliminate immune responses. Mechanistically, we have determined that DM editing in APC is a key event that is influenced by the kinetic stability of class II:peptide complexes and that differential persistence of complexes also impacts the expansion phase of the immune response. These studies have important implications for rational vaccine design and for understanding the immunological mechanisms that limit the specificity of CD4 T cell responses.