To test the hypothesis that chronic stimulation of T cells with a weak agonistic antigen will generate regulatory T cells and immune tolerance, a study reported in this issue employed the redesign of a minor histocompatibility antigen. Using knowledge of residues at which the antigen contacts the T cell receptor, a weak agonist was produced. Pretreatment with this altered antigen produced transplant tolerance, generation of regulatory T cells, and a loss of many antigen-reactive T cells.
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