The nature of the T cell response to minor histocompatibility antigens (miH) is poorly understood. These responses constitute an important part of the graft-vs-leukemia effect in bone marrow transplantation. A thorough understanding would help in the utilization of this effect in a more efficacious manner. A number of novel techniques, developed by the applicant, will enable the detailed study of the nature of miH. cDNA encoding miH, recognized by specific T cell clones, will be identified. The characteristics of the miH will be determined. This includes: a) The concordance, if any, between the previously functionally defined and actual chromosomal locations of miH loci. b) The identity of the donor miH protein and the definition and abundance of its naturally processed peptide products. c) The molecular basis of the antigenic polymorphism at the miH locus. d) Whether all or a subset of tissues express the miH peptide/MHC ligands. e) The immunodominance of individual miH as a function of their complexity and relative levels of expression. The data obtained should lead to new models and insights into the origin and role of immunodominant antigenic peptides in the context of complex cellular antigens.