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The specific elements in a T cell-dependentimmuneresponse to a protein are: the peptideantigen; the MHC molecule, which binds thepeptide antigen; and the cognate receptor ofthe T cell, which recognizes the peptide-MHCcomplex.Accessorycostimulatormoleculesarerequiredfor anormalimmuneresponsebutdonot account for its specificity and diversity.Therapyto modifyimmuneresponses in a spe-cific mannershould therefore logically be tar-getedto oneormoreofthesespecific elements.A range of strategies (Table 1) centered onantigen, MHC molecule, or T cell receptor(TCR) havebeen shownto prevent the induc-tion or favorably modifythe natural history ofautoimmunedisease inrodents. Strategies cen-tered on autoantigens have a clear advantagein humanautoimmune disease. Theoretically,autoantigen-based therapy is generic (i.e., ap-plicable to all individuals [who exhibit immu-nity, presumed pathogenic, to the autoanti-gen]), whereastheutility ofMHCmoleculesorTCRsat the populationlevel is limited bytheir

Antigen-Specific Therapy for Autoimmune Disease: Prospects for the Prevention of Insulin-Dependent Diabetes