Lowering the tone: mechanisms of immunodominance among epitopes with low affinity for MHC.

Past studies of immunodominance among T-cell epitopes have focused on peptides with high affinity for their restriction element, assuming epitopes of low affinity to be immunologically irrelevant. Here, Paul Fairchild and David Wraith challenge this assumption by reviewing evidence that such peptides may contribute to T-cell repertoire selection and autoimmune disease, and suggest approaches to immunotherapy based on exploitation of these peptides.