Expression pattern of agonist antigen influences timing of thymic selection (63.5)

Abstract

Abstract MHC complexes with peptides from minor histocompatibility (H) antigens which are naturally occurring polymorphic proteins are recognized by T cells. The mismatches at the Minor H loci induce allo-reactive T cell activation, leading to graft-rejection, graft-versus-host disease, or graft-versus-leukemia under MHC-matched transplantation circumstances. T cell response specific for H60 has been characterized as a dominant. In order to investigate the effect of antigenic expression pattern on the outcome of bone marrow transplantation, we generated a TCR transgenic mouse (named J15), of which specificity is H60 peptide in complexes with H2-Kb, with TCR α and β genes were originated a H60-specific CTL clone. The thymocytes in the J15 mice mostly developed to CD8 T lineage and showed proliferation in response to H60-stimulation. The thymocytes bearing J15 TCR were deleted in the mice where H60 are expressed in hematopoietic cell-restricted pattern and ubiquitously, that is in the F1 mice after crossing of J15 to H60 congenic (J15TgH60C/-) or to H60 transgenic mouse (J15TgAct-H60Tg), respectively. But the deletion timing was different during the double negative stages between the two F1 mice. The different deletion timing was observed when the bone marrow chimeras were generated with H60 congenic mice and with Act-H60Tg mice as hosts into which bone marrow from the J15 were transferred. These results demonstrate that antigen expression pattern influences the thymic selection timing.