Many self-antigens are expressed at a very low level that is insufficient to induce T-cell activation. In the case of T cells, which recognize short peptides associated with MHC molecules, the induction of self-tolerance requires the generation of a sufficient amount of self peptide in antigen-presenting cells to stimulate T-cell deletion or anergy. Self-peptides that are generated inefficiently by the antigen-presenting cells can neither stimulate immunity nor induce tolerance; that is, the immune system remains "ignorant" of them. If these minor self-peptides are produced in larger amounts and exposed to the immune system in the presence of an inducer of co-stimulatory molecules (eg adjuvants), they have the capacity to stimulate an immune response. This has been shown experimentally with peptides generated in vitro using proteolytic enzymes or using synthetic self peptides.
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