Molecules encoded by a single major histo- (7)(8)(9). These molecules can be exogenously loaded with a single type of synthetic peptide thereby creating a situation in which all class I-peptide complexes on the cell surface are identical. In a set of recent reports, we (10) and others (11) observed that loading unoccupied Kb molecules with different synthetic peptide antigens altered their recognition by alloantibodies. For instance, the Kb-specific monoclonal antibody (mAb) SF1.2 bound Kbovalbumin peptide complexes significantly better than empty Kb or Kb-Sendai (SV9) peptide complexes (10). In contrast, the Kb-specific mAb 100-30 reacted strongly to empty Kb or Kb-SV9 complexes but not to Kb-ovalbumin peptide complexes. These results suggested that the nature of the peptide bound to the class I molecule influenced alloantibody recognition. However, such results were obtained using synthetic antigens, some of which were much longer than endogenous peptides that are generally eight or nine residues long. Based on these results, as well as the observation by several laboratories that antibodies can be specific for certain MHC-