Biochemical and immunogenetic analysis of an immunodominant peptide (B6(dom1)) encoded by the classical H7 minor histocompatibility locus

Of the many minor histocompatibility (H) Ags that have been detected in mic e, the ability to induce graft vs host disease (GVHD) after bone marrow tra nsplantation is restricted to a limited number of immunodominant,Ags. One s uch mutine Ag, B6(dom1), is presented by the H2-D-h MHC class I molecule. W e present biochemical evidence that the natural B6(dom1) peptide is indisti nguishable from AAPDNRETF, and we show that this peptide ran be isolated fr om a wide array of tissues, with highest levels from the lymphoid organs an d lung. Moreover, we employ a novel, somatic cell selection technique invol ving CTL-mediated immunoselection coupled with classical genetics, to show that B6(dom1) is encoded by the H7 minor H locus originally- discovered sim ilar to 40 years ago. These studies provide a molecular genetic framework f or understanding B6(dom1) and exemplify the fact that mouse minor H loci th at encode immunodominant CTL epitopes can correspond to classical H loci or iginally identified by their ability to confer strong resistance to tumor t ransplantation, additionally. these studies demonstrate the utility of soma tic cell selection approaches toward resolving H Ag Immunogenetics.