In this issue of the JCI, two separate studies on MHC-bound peptides reopen the debate on the utility of peptides for the purposes of vaccination and treatment of autoimmune diseases. In the first study, by Wahlström et al., peptides bound to HLA-DR17 from bronchoalveolar lavage cells of sarcoidosis patients were analyzed in order to identify target antigens of the autoimmune response (see the related article beginning on page 3576). In the second study, by Le Gall et al., the modulation of epitope immunodominance and the processing and presentation of HIV peptides for MHC class I recognition were shown to be dependent on flanking residues that were N terminal to the natural epitopes (see the related article beginning on page 3563). Both studies highlight the tremendous therapeutic potential of MHC-bound peptides. They also emphasize that technical issues are still plaguing this field and hindering our understanding of MHC presentation in vivo.