The long term goal of this project is to define the molecular basis of the immune responses that mediate graft versus host disease in MHC identical unrelated bone marrow transplants. The investigator will also define protocols for specific suppression of immunity to allo-antigens without compromising the function of all T cells. The investigator wishes to define the mechanism of immunodominance to minor histocompatibility (mH) antigens in molecular terms and to develop novel protocols to induce transplant tolerance. The rationale behind this research is that the molecular basis of immunodominance to mH antigens is poorly understood. Additionally, current protocols for immuno- suppression affect all activated T cells or T-cell subsets, thereby paralyzing immune responses to pathogens. The investigator will test 2 hypotheses: First, that immunodominance is determined in great part by CTL precursor frequency, affinity of peptide to MHC and the affinity of MHC/peptide complexes for the TcR. The second hypothesis to be tested is that immunity to mH antigens can be inhibited by soluble tetrameric class I MHC molecules presenting a mH Ag-specific epitope. The expectation is that upon successful completion of the project, the investigator will have defined the molecular basis of immunodominance to antigens that elicit CTL responses in general, and that a novel protocol to down regulate CTL responses without general suppression will be developed.
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